Cancer, Solid TumorPhase 1KEYNOTE-001NCT01295827

Study of Pembrolizumab (MK-3475) in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/MK-3475-001/KEYNOTE-001)

A Phase 1 study testing Pembrolizumab in people with Cancer, Solid Tumor, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Cancer, Solid Tumor
What is being tested?: Pembrolizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,260 participants
Where: No sites listed yet
Study dates: 4 Mar 2011to 11 Dec 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

In Part A: Histological or cytological diagnosis of MEL or any type of carcinoma, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. In Parts B and D of the study, histological or cytological diagnoses of metastatic MEL with progressive locally advanced or metastatic disease. In Parts C and F, histological or cytological diagnosis of NSCLC. In Part F1, participants with Stage IV NSCLC without prior systemic therapy may be eligible.
Failure of established standard medical anti-cancer therapies for a given tumor type or intolerance to such therapy.
In Parts B, C, D, or F of the study, MEL or NSCLC must be measurable by imaging.
In Part F of the study, NSCLC with PD-L1 gene expression.
Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
Adequate organ function.

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Female participants of childbearing potential should have a negative urine or serum pregnancy test prior to receiving study medication
Female participants of childbearing potential must be willing to use adequate contraception from study start, through the course of the study, and for 120 days after the last dose of study medication
Male participants of childbearing potential must agree to use adequate contraception from the first dose of study medication through 120 days after the last dose of study medication

Who cannot join

Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the adverse events caused by therapy administered more than 4 weeks prior to first dose.
Participation in a study of an investigational agent or using an investigational device within 30 days of administration of pembrolizumab, with the exception of participants in the follow-up phase.
Other form(s) of antineoplastic therapy anticipated during the period of the study.
History of non-infectious pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease.
Medical condition that requires chronic systemic steroid therapy, or on any other form of immunosuppressive medication, excepting use of inhaled steroids.
Risk factors for bowel obstruction or bowel perforation (including a history of acute diverticulitis, intra-abdominal abscess, abdominal carcinomatosis).

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History of a hematologic malignancy, malignant primary brain tumor, malignant sarcoma, or another malignant primary solid tumor, unless no evidence of that disease for 5 years.
Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Previous severe hypersensitivity reaction to another monoclonal antibody (mAb).
Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents, except vitiligo or resolved childhood asthma/atopy.
Prior therapy with another anti-programmed cell death (PD)-1 agent or previously enrolled in any pembrolizumab trial.
Active infection requiring therapy.
Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen [HBsAg] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid [HCV RNA] (qualitative) is detected).
Regular use of illicit drugs or a recent history (within the last year) of substance abuse (including alcohol).
Symptomatic ascites or pleural effusion.
Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.

About this study

Official title: Phase I Study of Single Agent Pembrolizumab (MK-3475) in Patients With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, and Non-Small Cell Lung Carcinoma (KEYNOTE 001)

The present study has 5 parts. In Parts A and A1, the dose of intravenous (IV) pembrolizumab (MK-3475) will be escalated from 1 to 10 mg/kg to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for participants with a histologically- or cytologically-confirmed diagnosis of any type of carcinoma or melanoma (MEL) by evaluating the Dose Limiting Toxicities (DLTs). Following completion of the dose escalation, additional patients will be enrolled in Part A2 to further define pharmacokinetic characteristics. Part B of the study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL and compare every 2 week dosing (Q2W) to every 3 week dosing (Q3W). Part C of the study will investigate the safety, tolerability, and efficacy of pembrolizumab administered at 10 mg/kg Q3W in participants with non-small cell lung carcinoma (NSCLC) that is locally advanced or metastatic. Part D of the study will investigate the low and high doses of study drug identified in Parts A and B (2 mg/kg and 10 mg/kg) administered Q3W in participants with advanced or metastatic MEL. Part E (closed with Amendment 7) was planned to investigate low, medium, and high doses of pembrolizumab in combination with standard chemotherapy in participants with locally advanced or metastatic NSCLC. Part F will investigate low and high doses of pembrolizumab (2 mg/kg and 10 mg/kg) administered Q2W or Q3W in treatment-naive and previously-treated participants with NSCLC with programmed cell death 1 ligand (PD-L1) gene expression. The primary hypotheses are the following: that pembrolizumab will have acceptable safety and tolerability; that pembrolizumab will show a clinically meaningful response rate (RR) or disease-control rate (DCR) in participants with melanoma (ipilimumab-refractory or not) and NSCLC, and that pembrolizumab will show a more clinically meaningful RR in participants with either cancer whose tumors express PD-L1.

Read the detailed description

Per protocol, all participants who were receiving study intervention or in survival follow-up could enroll in the extension study, KEYNOTE-587 (NCT03486873), which would allow further study participation after the Primary Completion Date cut-off. Thus, all efficacy outcome measures except for survival (Overall Survival [OS]) were to be followed up to the Interim Database cut-off of 18-Sept-2018, and the primary safety analyses (except for the DLT analysis) and Overall Survival were to be followed up to the study Primary Completion Date (Final Database cut-off of 05-Nov-2018).

Five participants did not have end of study assessments completed by the Primary Completion Date cut-off and were subsequently followed up to the Study Completion Date (11-Dec-2018). End of treatment and end of study assessments are missing for these 5 and the status was noted as unknown as of the Primary Completion Date cut-off. Per protocol, any safety information after the Primary Completion Date cut-off (Final Database cut-off of 05-Nov-2018) would not be included in the safety analysis but reported by the Investigator to the Sponsor via the Sponsor Communication Form and filed in the electronic Trial Master File.

Conditions: Cancer, Solid Tumor
Being tested: Pembrolizumab
Keywords: Melanoma, Carcinoma, Cancer, Advanced cancer, Metastatic cancer, Metastatic melanoma, Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Medical subject headings: Neoplasms, Melanoma, Carcinoma, Neoplasm Metastasis, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
IV infusion over 30 minutes on Day 1 of each cycle, administered according to dose selection or randomization.

Study groups in NCT01295827
Study group	Role	What they receive
Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A)	Experimental	During Cycle 1 participants received a dose of 1 mg/kg pembrolizumab intravenous (IV) infusion over 30 minutes on Day 1 of a 28-day cycle for evaluation of dose-limiting toxicities and pharmacokinetics. Participants received pembrolizumab IV at a dose of 1 mg/kg every 2 weeks (Q2W) starting with Cycle 2. Receives: Biological: Pembrolizumab
Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A)	Experimental	During Cycle 1 participants received a dose of 3 mg/kg pembrolizumab IV infusion over 30 minutes on Day 1 of a 28-day cycle for evaluation of dose-limiting toxicities and pharmacokinetics. Participants received pembrolizumab IV at a dose of 3 mg/kg Q2W starting with Cycle 2. Receives: Biological: Pembrolizumab
Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1)	Experimental	During Cycle 1 participants received a dose of 10 mg/kg pembrolizumab IV infusion over 30 minutes on Day 1 of a 28-day cycle for evaluation of dose-limiting toxicities and pharmacokinetics. Participants received pembrolizumab IV at a dose of 10 mg/kg Q2W starting with Cycle 2. Receives: Biological: Pembrolizumab
Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2)	Experimental	During Cycle 1 participants received pembrolizumab dose titration from 0.005 mg/kg to 0.3 mg/kg to 2.0 mg/kg on Days 1, 8, and 22, administered as an IV infusion over 30 minutes. Participants received 2 mg/kg every 3 weeks (Q3W) starting with Cycle 2. Receives: Biological: Pembrolizumab
Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2)	Experimental	During Cycle 1 participants received pembrolizumab dose titration from 0.02 mg/kg to 0.3 mg/kg to 2.0 mg/kg on Days 1, 8, and 22, administered as an IV infusion over 30 minutes. Participants received 2 mg/kg Q3W starting with Cycle 2. Receives: Biological: Pembrolizumab
Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2)	Experimental	During Cycle 1 participants received pembrolizumab dose titration from 0.06 mg/kg to 1.0 mg/kg to 10 mg/kg on Days 1, 8, and 22, administered as an IV infusion over 30 minutes. Participants received 10 mg/kg Q3W starting with Cycle 2. Receives: Biological: Pembrolizumab
MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D)	Experimental	Participants received pembrolizumab IV at a dose of 2 mg/kg Q2W. After Amendment 3, participants received dosing Q3W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data. Receives: Biological: Pembrolizumab
MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D)	Experimental	Participants received pembrolizumab IV at a dose of 10 mg/kg Q2W. After Amendment 7, participants received dosing Q3W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data. Receives: Biological: Pembrolizumab
MEL: Pembrolizumab 10 mg/kg Q2W (Part B)	Experimental	Participants received pembrolizumab IV at a dose of 10 mg/kg Q2W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data. Receives: Biological: Pembrolizumab
NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F)	Experimental	Participants received pembrolizumab IV at a dose of 2 mg/kg Q3W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data. Receives: Biological: Pembrolizumab
NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F)	Experimental	Participants received pembrolizumab IV at a dose of 10 mg/kg Q3W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data. Receives: Biological: Pembrolizumab
NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F)	Experimental	Participants received pembrolizumab IV at a dose of 10 mg/kg Q2W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data. Receives: Biological: Pembrolizumab
NSCLC: Pembrolizumab 2 mg/kg Q3W (Part E-Not Enrolled)	Experimental	Participants were to receive pembrolizumab IV at a dose of 2 mg/kg Q3W. No participants were enrolled in this arm. Receives: Biological: Pembrolizumab
NSCLC: Pembrolizumab 5 mg/kg Q3W (Part E-Not Enrolled)	Experimental	Participants were to receive pembrolizumab IV at a dose of 5 mg/kg Q3W. No participants were enrolled in this arm. Receives: Biological: Pembrolizumab
NSCLC: Pembrolizumab 10 mg/kg Q3W (Part E-Not Enrolled)	Experimental	Participants were to receive pembrolizumab IV at a dose of 10 mg/kg Q3W. No participants were enrolled in this arm. Receives: Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) in Participants With Solid Tumors (Parts A and A1)
DLTs were assessed according to NCI-CTCAE v.4.0 during the first cycle (28 days) and were defined as occurrence of any of the following toxicities if judged by the investigator to be possibly, probably or definitely related to study drug administration: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥14 days; Gr 3 nonhematologic toxicity lasting >3 days despite optimal supportive care; any Grade 3 non-hematologic laboratory value if medical intervention was required to treat the participant, the abnormality led to hospitalization, or the abnormality persisted for >1 week; Gr 3 or 4 febrile neutropenia; thrombocytopenia <25,000 cells/mm^3 (if associated with a bleeding event requiring an elective platelet transfusion, or a life-threatening bleeding event which resulted in urgent intervention and admission to an Intensive Care Unit); or Gr 5 toxicity. The number of participants in Part A and Part A1 with a DLT were reported by pembrolizumab dose received.
Measured: Up to 28 days in Cycle 1
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced an AE was reported for each arm.
Measured: Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018)
Overall Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Integrated Radiology and Oncology (IRO): Melanoma Participants (Parts B Plus D)
ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRO was reported as the ORR for each melanoma dose arm (Parts B plus D).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
ORR According to RECIST 1.1 as Assessed by Independent Review Committee (IRC): Non-Small Cell Lung Cancer (NSCLC) Participants (Parts C Plus F)
ORR was defined as the percentage of participants in the analysis population who had a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRC was reported as the ORR for each NSCLC dose arm (Parts C plus F).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)

Secondary outcomes (28)

ORR According to Immune-related Response Criteria (irRC) as Assessed by Investigator in Melanoma Participants (Parts B Plus D)
ORR was defined as the percentage of participants in the analysis population who had a confirmed immune-related Complete Response (irCR: complete disappearance of all tumor lesions whether measurable or not, and no new lesions) or immune-related Partial Response (irPR: decrease in sum of the products of the two largest perpendicular diameters (SPD) of ≥50% by a consecutive assessment ≥4 weeks after first documentation) according to irRC. The percentage of participants who experienced a confirmed irCR or irPR according to irRC as assessed by the investigator was reported as the ORR for each melanoma dose arm (Parts B plus D).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
ORR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F)
ORR was defined as the percentage of participants in the analysis population who had a confirmed irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions) or irPR (decrease in sum of the products of the two largest perpendicular diameters (SPD) of ≥50% by a consecutive assessment ≥4 weeks after first documentation) according to irRC. The percentage of participants who experienced a confirmed irCR or irPR according to irRC as assessed by the investigator was reported as the ORR for each NSCLC dose arm (Parts C plus F).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Day 28 (AUC 0-28) in Solid Tumor Participants (Parts A and A1)
Blood samples were collected at specified intervals for the determination of AUC0-28. AUC0-28 was defined as the area under the concentration-time curve of pembrolizumab from time zero to Day 28. AUC0-28 was based on noncompartmental analysis and reported for participants in Parts A and A1.
Measured: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Infinity (AUC 0-inf) in Solid Tumor Participants (Parts A and A1)
Blood samples were collected at specified intervals for the determination of AUC0-inf. AUC0-inf was defined as the area under the concentration-time curve of pembrolizumab from time zero to infinity. AUC0-inf was based on noncompartmental analysis and reported for participants in Parts A and A1.
Measured: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Maximum Concentration (Cmax) of Pembrolizumab in Solid Tumor Participants (Parts A and A1)
Blood samples were collected at specified intervals for the determination of Cmax. Cmax was defined as the maximum concentration of pembrolizumab reached. Cmax was based on noncompartmental analysis and reported for participants in Parts A and A1.
Measured: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Time to Maximum Concentration (Tmax) of Pembrolizumab in Solid Tumor Participants (Parts A and A1)
Blood samples were collected at specified intervals for the determination of Tmax. Tmax was defined as time to the maximum concentration of pembrolizumab reached. Tmax was based on noncompartmental analysis and reported for participants in Parts A and A1.
Measured: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Terminal Half-Life (t ½) of Pembrolizumab in Solid Tumor Participants (Parts A and A1)
Blood samples were collected at specified intervals for the determination of t½. t½ was defined as the time required to divide the pembrolizumab plasma concentration by two after reaching pseudo-equilibrium, following a single dose of pembrolizumab. t½ was based on noncompartmental analysis and reported for participants in Parts A and A1.
Measured: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Day 21 (AUC 0-21) in Solid Tumor Participants (Part A2)
Blood samples were collected at specified intervals for the determination of AUC0-21. AUC0-21 was defined as the area under the concentration-time curve of pembrolizumab from time zero to Study Day 21. AUC0-21 was based on noncompartmental analysis and reported for participants in Part A2.
Measured: Cycle 1: Day 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours; Day 5, Day 8: pre- and post-dose; Day 15 (Cycle = 21 days)
Area Under the Concentration-Time Curve of Pembrolizumab From Day 21 to Day 42 (AUC21-42) in Solid Tumor Participants (Part A2)
Blood samples were collected at specified intervals for the determination of AUC21-42. AUC21-42 was defined as the area under the concentration-time curve of pembrolizumab from Study Day 21 (end of Cycle 1) through Study Day 42 (end of Cycle 2). AUC21-42 was based on noncompartmental analysis and reported for participants in Part A2.
Measured: Cycle 1: Day 21; Cycle 2: Day 1: Pre-dose, post-dose at 0.5 and 24 hours, Day 3, Day 8, Day 15 (Cycle = 21 days)
Lowest Plasma Concentration (Ctrough) of Pembrolizumab in Solid Tumor Participants (Parts A, A1, and A2)
Pre-dose samples were collected 24 hours before infusion of pembrolizumab at specified intervals for the determination of Ctrough. Ctrough was defined as the lowest concentration of pembrolizumab reached before the next dose was administered. Ctrough was reported for each Part A arm according to cycle and nominal time after first dose (Day). Results for each cycle reported for arms with N>1 at that timepoint. Ctrough data for melanoma (Parts B and D) and NSCLC (Parts C and F) participants are presented separately and are not included here.
Measured: Parts A and A1: pre-dose at Cycles 2, 4, 6, 8, 10, 12, 14 (cycle=14 days); A2 Cohorts: pre-dose at Cycles 2, 3, 5, 7, 9, 11 (cycle=21 days)
Ctrough of Pembrolizumab in Melanoma Participants (Parts B and D)
Pre-dose samples were collected 24 hours before infusion of pembrolizumab at specified intervals for the determination of Ctrough. Ctrough was defined as the lowest concentration of pembrolizumab reached before the next dose was administered. For the purposes of the Ctrough analysis, samples were collected and analyzed separately for each Part B and D enrolment cohort, and Ctrough was reported for each cohort according to cycle and nominal time after first dose (Day). Results for each cycle reported for arms with N>1 at that timepoint. Ctrough data for solid tumor (Part A) and NSCLC (Parts C and F) participants are presented separately and are not included here.
Measured: Part B arms treated every 3 weeks: pre-dose at Cycles 2,5,9,13,17,25,33 (cycle=21 days); Part B treated every 2 weeks: pre-dose at Cycles 2,3,7,13,19,25,31,37 (cycle=14 days); Part D: pre-dose at Cycles 2,3,6,8,12,16,24,32 (cycle=21 days)
Ctrough of Pembrolizumab in NSCLC Participants (Parts C and F)
Pre-dose samples were collected 24 hours before infusion of pembrolizumab at specified intervals for the determination of Ctrough. Ctrough was defined as the lowest concentration reached by pembrolizumab before the next dose was administered. For the purposes of the Ctrough analysis, samples were collected and analyzed separately for each Part C and F enrolment cohort, and Ctrough was reported for each cohort according to cycle and nominal time after first dose (Day). Results for each cycle reported for arms with N>1 at that timepoint. Ctrough data for solid tumor (Part A) and melanoma (Parts B and D) participants are presented separately and are not included here.
Measured: Part C: pre-dose at Cycles 2,5,9,13,17,21 (cycle=21 days); Part F treated every 3 weeks: pre-dose at Cycles 2,3,6,8,12,14,16,24,32 (cycle=21 days); Part F treated every 2 weeks: pre-dose at Cycles 2,3,6,7,8,9,12,16,18,24,32,36,40,48 (cycle=14 days)
Maximum Change From Baseline (CFB) in Tumor Size Assessed by IRC Per RECIST 1.1 According to Programmed Death-Ligand 1 (PD-L1) Immunohistochemical (IHC) Expression Status in Ipilimumab (Ipi)-Exposed and Ipi-Naive Melanoma Participants (Parts B Plus D)
The percent change from baseline in tumor size based on IRC per RECIST 1.1 was reported according to PD-L1 status in Ipi-Exposed and Ipi-Naïve melanoma participants. Tumor PD-L1 status was measured by the tumor proportion score (TPS), which was the percentage of tumor cells identified using IHC analysis that expressed PD-L1. Tumors with ≥1% positive staining for PD-L1 were considered positive. Maximum tumor change was defined as the percent change of the participant's smallest post-baseline tumor size from the baseline. The number of participants in a percent change from baseline range was reported categorically according to PD-L1 status (PD-L1-Positive, PD-L1 Negative, PD-L1 Status Unknown). Negative percent change from baseline values indicate tumor size reduction, with the greatest reduction possible indicated as "≤ -30%". As specified by the protocol, this analysis of melanoma participants was performed according to ipilimumab exposure (Ipi-Exposed and Ipi-Naïve).
Measured: Baseline, last available tumor assessment (up to approximately 53 months through Interim Database cut-off date of 18-Sep-2015)
Maximum Change From Baseline (CFB) in Tumor Size Assessed by IRC Per RECIST 1.1 According to PD-L1 IHC Expression Status in Prior Treatment (TRT)-Naïve and Previously-Treated NSCLC Participants (Parts C Plus F)
Percent CFB in tumor size based on IRC per RECIST 1.1 was reported according to PD-L1 status in prior treatment-naïve and previously-treated NSCLC participants. Tumor PD-L1 status was measured by TPS, which was the percentage of tumor cells identified using IHC analysis that expressed PD-L1, as follows: TPS ≥50% =tumor strongly positive, TPS of 1%-49% =tumor weakly positive, TPS <1% =tumor considered negative, or TPS unknown. Maximum tumor change for a participant was defined as the percent change of the participant's smallest post-baseline tumor size from baseline. The number of participants in a percent CFB range was reported categorically according to PD-L1 status (TPS ≥50%, TPS = 1-49%, TPS <1%, TPS Unknown). Negative percent CFB values indicate tumor size reduction, with the greatest reduction possible indicated as "≤ -30%". As specified by the protocol, analysis of NSCLC participants was performed according to prior treatment exposure (Treatment Naive and Previously Treated).
Measured: Baseline, last available tumor assessment (up to approximately 53 months through Interim Database cut-off date of 18-Sep-2015)
Disease Control Rate (DCR) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B and D)
DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by IRO was reported as the DCR for each melanoma dose arm (Parts B plus D).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
Duration of Response (DOR) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B and D)
For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on IRO with confirmation. The DOR according to RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported for each melanoma dose arm (Parts B plus D).
Measured: From time of first documented evidence of CR or PR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months)
Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B Plus D)
PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS according to RECIST 1.1 as assessed by IRO was reported for each melanoma dose arm (Parts B plus D).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
Overall Survival (OS) in Melanoma Participants (Parts B Plus D)
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. OS was reported for each melanoma dose arm (Parts B plus D).
Measured: Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018)
DCR According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D)
DCR according to irRC was defined as the percentage of participants who had a irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions), irPR (decrease in SPD of ≥50% by a consecutive assessment ≥4 weeks after first documentation), or SD (neither sufficient shrinkage to qualify for irPR nor sufficient increase to qualify for PD [at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented]). The percentage of participants who experienced a confirmed CR, PR, or SD according to irRC as assessed by the investigator was reported as the DCR for each melanoma dose arm (Parts B plus D).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
DOR According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D)
For participants who demonstrated a confirmed irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions) or irPR (decrease in SPD of ≥50% by a consecutive assessment ≥4 weeks after first documentation) according to irRC, DOR was defined as the time from first documented evidence of an irCR or irPR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. According to irRC, PD was defined as at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented. The DOR according to irRC as assessed by the investigator for all participants who experienced a confirmed irCR or irPR was reported for each melanoma dose arm (Parts B plus D).
Measured: From time of first documented evidence of iCR or iPR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months)
PFS According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D)
PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. According to irRC, PD was defined as at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented. PFS according to irRC as assessed by the investigator was reported for each melanoma dose arm (Parts B plus D).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
DCR According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F)
DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by IRC was reported as the DCR for each NSCLC dose arm (Parts C plus F).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
DOR According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F)
For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on IRC with confirmation. The DOR according to RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported for each NSCLC dose arm (Parts C plus F).
Measured: From time of first documented evidence of CR or PR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months)
PFS According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F)
PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS according to RECIST 1.1 as assessed by IRC was reported for each NSCLC dose arm (Parts C plus F).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
OS in NSCLC Participants (Parts C Plus F)
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. OS was reported for each NSCLC dose arm (Parts C plus F).
Measured: Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018)
DCR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F)
DCR according to irRC was defined as the percentage of participants who had a irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions), irPR (decrease in SPD of ≥50% by a consecutive assessment ≥4 weeks after first documentation), or SD (neither sufficient shrinkage to qualify for irPR nor sufficient increase to qualify for PD [at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented]). The percentage of participants who experienced a confirmed CR, PR, or SD according to irRC as assessed by the investigator was reported as the DCR for each NSCLC dose arm (Parts C plus F).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
DOR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F)
For participants who demonstrated a confirmed irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions) or irPR (decrease in SPD of ≥50% by a consecutive assessment ≥4 weeks after first documentation) according to irRC, DOR was defined as the time from first documented evidence of an irCR or irPR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. According to irRC, PD was defined as at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented. The DOR according to irRC as assessed by the investigator for all participants who experienced a confirmed irCR or irPR was reported for each NSCLC dose arm (Parts C plus F).
Measured: From time of first documented evidence of iCR or iPR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months)
PFS According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F)
PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. According to irRC, PD was defined as at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented. PFS according to irRC as assessed by the investigator was reported for each NSCLC dose arm (Parts C plus F).
Measured: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Mar 201111 Dec 2018

First posted15 Feb 2011 (estimated)
Study start4 Mar 2011
Primary completion5 Nov 2018
Study completion11 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (24)Papers the sponsor has linked to this study.
Other trials for Cancer, Solid TumorStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 1,260 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01295827
Sponsor's protocol ID: P07990
Other IDs: MK-3475-001, 2011-002371-42, P07990, KEYNOTE-001
Acronym: KEYNOTE-001
Status last verified: Nov 2019
First submitted: 10 Feb 2011
Last updated: 13 Dec 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC, Patnaik A, Dronca R, Zarour H, Joseph RW, Boasberg P, Chmielowski B, Mateus C, Postow MA, Gergich K, Elassaiss-Schaap J, Li XN, Iannone R, Ebbinghaus SW, Kang SP, Daud A. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014 Sep 20;384(9948):1109-17. doi: 10.1016/S0140-6736(14)60958-2. Epub 2014 Jul 15.
PubMed 25034862
Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, Drengler R, Chen C, Smith L, Espino G, Gergich K, Delgado L, Daud A, Lindia JA, Li XN, Pierce RH, Yearley JH, Wu D, Laterza O, Lehnert M, Iannone R, Tolcher AW. Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Clin Cancer Res. 2015 Oct 1;21(19):4286-93. doi: 10.1158/1078-0432.CCR-14-2607. Epub 2015 May 14.
PubMed 25977344
Chatterjee M, Turner DC, Felip E, Lena H, Cappuzzo F, Horn L, Garon EB, Hui R, Arkenau HT, Gubens MA, Hellmann MD, Dong D, Li C, Mayawala K, Freshwater T, Ahamadi M, Stone J, Lubiniecki GM, Zhang J, Im E, De Alwis DP, Kondic AG, Flotten O. Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Ann Oncol. 2016 Jul;27(7):1291-8. doi: 10.1093/annonc/mdw174. Epub 2016 Apr 26.
PubMed 27117531
Topp BG, Channavazzala M, Mayawala K, De Alwis DP, Rubin E, Snyder A, Wolchok JD, Ribas A. Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression. Cancer Cell. 2023 Sep 11;41(9):1680-1688.e2. doi: 10.1016/j.ccell.2023.08.004.
PubMed 37699333
Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.
PubMed 35101941
Hamid O, Robert C, Daud A, Carlino MS, Mitchell TC, Hersey P, Schachter J, Long GV, Hodi FS, Wolchok JD, Arance A, Grob JJ, Joshua AM, Weber JS, Mortier L, Jensen E, Diede SJ, Moreno BH, Ribas A. Long-term outcomes in patients with advanced melanoma who had initial stable disease with pembrolizumab in KEYNOTE-001 and KEYNOTE-006. Eur J Cancer. 2021 Nov;157:391-402. doi: 10.1016/j.ejca.2021.08.013. Epub 2021 Sep 25.
PubMed 34571336
Robert C, Hwu WJ, Hamid O, Ribas A, Weber JS, Daud AI, Hodi FS, Wolchok JD, Mitchell TC, Hersey P, Dronca R, Joseph RW, Boutros C, Min L, Long GV, Schachter J, Puzanov I, Dummer R, Lin J, Ibrahim N, Diede SJ, Carlino MS, Joshua AM. Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma. Eur J Cancer. 2021 Feb;144:182-191. doi: 10.1016/j.ejca.2020.11.010. Epub 2020 Dec 24.
PubMed 33360855
Lala M, Li TR, de Alwis DP, Sinha V, Mayawala K, Yamamoto N, Siu LL, Chartash E, Aboshady H, Jain L. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020 May;131:68-75. doi: 10.1016/j.ejca.2020.02.016. Epub 2020 Apr 15.
PubMed 32305010
van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.
PubMed 31395089
Garon EB, Hellmann MD, Rizvi NA, Carcereny E, Leighl NB, Ahn MJ, Eder JP, Balmanoukian AS, Aggarwal C, Horn L, Patnaik A, Gubens M, Ramalingam SS, Felip E, Goldman JW, Scalzo C, Jensen E, Kush DA, Hui R. Five-Year Overall Survival for Patients With Advanced Non-Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol. 2019 Oct 1;37(28):2518-2527. doi: 10.1200/JCO.19.00934. Epub 2019 Jun 2.
PubMed 31154919
Leighl NB, Hellmann MD, Hui R, Carcereny E, Felip E, Ahn MJ, Eder JP, Balmanoukian AS, Aggarwal C, Horn L, Patnaik A, Gubens M, Ramalingam SS, Lubiniecki GM, Zhang J, Piperdi B, Garon EB. Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. Lancet Respir Med. 2019 Apr;7(4):347-357. doi: 10.1016/S2213-2600(18)30500-9. Epub 2019 Mar 12.
PubMed 30876831
Wang M, Chen C, Jemielita T, Anderson J, Li XN, Hu C, Kang SP, Ibrahim N, Ebbinghaus S. Are tumor size changes predictive of survival for checkpoint blockade based immunotherapy in metastatic melanoma? J Immunother Cancer. 2019 Feb 8;7(1):39. doi: 10.1186/s40425-019-0513-4.
PubMed 30736858
Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph R, Weber JS, Dronca R, Mitchell TC, Patnaik A, Zarour HM, Joshua AM, Zhao Q, Jensen E, Ahsan S, Ibrahim N, Ribas A. Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Ann Oncol. 2019 Apr 1;30(4):582-588. doi: 10.1093/annonc/mdz011.
PubMed 30715153
Hamid O, Robert C, Ribas A, Hodi FS, Walpole E, Daud A, Arance AS, Brown E, Hoeller C, Mortier L, Schachter J, Long J, Ebbinghaus S, Ibrahim N, Butler M. Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc analysis of KEYNOTE-001, 002, 006. Br J Cancer. 2018 Sep;119(6):670-674. doi: 10.1038/s41416-018-0207-6. Epub 2018 Sep 11.
PubMed 30202085
Joseph RW, Elassaiss-Schaap J, Kefford R, Hwu WJ, Wolchok JD, Joshua AM, Ribas A, Hodi FS, Hamid O, Robert C, Daud A, Dronca R, Hersey P, Weber JS, Patnaik A, de Alwis DP, Perrone A, Zhang J, Kang SP, Ebbinghaus S, Anderson KM, Gangadhar TC. Baseline Tumor Size Is an Independent Prognostic Factor for Overall Survival in Patients with Melanoma Treated with Pembrolizumab. Clin Cancer Res. 2018 Oct 15;24(20):4960-4967. doi: 10.1158/1078-0432.CCR-17-2386. Epub 2018 Apr 23.
PubMed 29685882

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Questions to ask the study team

What is the study trying to find out?
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Official record

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Cancer, Solid Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Study of Single Agent Pembrolizumab (MK-3475) in Patients With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, and Non-Small Cell Lung Carcinoma (KEYNOTE 001)
ClinicalTrials.gov ID: NCT01295827
Acronym / sponsor ID: KEYNOTE-001 / P07990
Conditions: Cancer, Solid Tumor
Keywords: Melanoma, Carcinoma, Cancer, Advanced cancer, Metastatic cancer, Metastatic melanoma, Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,260 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 4 Mar 2011 (actual)
Primary completion: 5 Nov 2018 (actual)
Study completion: 11 Dec 2018 (actual)
First posted: 15 Feb 2011 (estimated)
Results: Posted 13 Dec 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 15

Arm	Type	Receives
Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A)	Experimental	Biological: PembrolizumabDuring Cycle 1 participants received a dose of 1 mg/kg pembrolizumab intravenous (IV) infusion over 30 minutes on Day 1 of a 28-day cycle for evaluation of dose-limiting toxicities and pharmacokinetics. Participants received pembrolizumab IV at a dose of 1 mg/kg every 2 weeks (Q2W) starting with Cycle 2.
Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A)	Experimental	Biological: PembrolizumabDuring Cycle 1 participants received a dose of 3 mg/kg pembrolizumab IV infusion over 30 minutes on Day 1 of a 28-day cycle for evaluation of dose-limiting toxicities and pharmacokinetics. Participants received pembrolizumab IV at a dose of 3 mg/kg Q2W starting with Cycle 2.
Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1)	Experimental	Biological: PembrolizumabDuring Cycle 1 participants received a dose of 10 mg/kg pembrolizumab IV infusion over 30 minutes on Day 1 of a 28-day cycle for evaluation of dose-limiting toxicities and pharmacokinetics. Participants received pembrolizumab IV at a dose of 10 mg/kg Q2W starting with Cycle 2.
Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2)	Experimental	Biological: PembrolizumabDuring Cycle 1 participants received pembrolizumab dose titration from 0.005 mg/kg to 0.3 mg/kg to 2.0 mg/kg on Days 1, 8, and 22, administered as an IV infusion over 30 minutes. Participants received 2 mg/kg every 3 weeks (Q3W) starting with Cycle 2.
Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2)	Experimental	Biological: PembrolizumabDuring Cycle 1 participants received pembrolizumab dose titration from 0.02 mg/kg to 0.3 mg/kg to 2.0 mg/kg on Days 1, 8, and 22, administered as an IV infusion over 30 minutes. Participants received 2 mg/kg Q3W starting with Cycle 2.
Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2)	Experimental	Biological: PembrolizumabDuring Cycle 1 participants received pembrolizumab dose titration from 0.06 mg/kg to 1.0 mg/kg to 10 mg/kg on Days 1, 8, and 22, administered as an IV infusion over 30 minutes. Participants received 10 mg/kg Q3W starting with Cycle 2.
MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D)	Experimental	Biological: PembrolizumabParticipants received pembrolizumab IV at a dose of 2 mg/kg Q2W. After Amendment 3, participants received dosing Q3W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data.
MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D)	Experimental	Biological: PembrolizumabParticipants received pembrolizumab IV at a dose of 10 mg/kg Q2W. After Amendment 7, participants received dosing Q3W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data.
MEL: Pembrolizumab 10 mg/kg Q2W (Part B)	Experimental	Biological: PembrolizumabParticipants received pembrolizumab IV at a dose of 10 mg/kg Q2W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data.
NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F)	Experimental	Biological: PembrolizumabParticipants received pembrolizumab IV at a dose of 2 mg/kg Q3W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data.
NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F)	Experimental	Biological: PembrolizumabParticipants received pembrolizumab IV at a dose of 10 mg/kg Q3W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data.
NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F)	Experimental	Biological: PembrolizumabParticipants received pembrolizumab IV at a dose of 10 mg/kg Q2W. After Amendment 10, all remaining and ongoing participants were treated with a 200 mg fixed dose of pembrolizumab IV Q3W based on analysis of safety and efficacy data.
NSCLC: Pembrolizumab 2 mg/kg Q3W (Part E-Not Enrolled)	Experimental	Biological: PembrolizumabParticipants were to receive pembrolizumab IV at a dose of 2 mg/kg Q3W. No participants were enrolled in this arm.
NSCLC: Pembrolizumab 5 mg/kg Q3W (Part E-Not Enrolled)	Experimental	Biological: PembrolizumabParticipants were to receive pembrolizumab IV at a dose of 5 mg/kg Q3W. No participants were enrolled in this arm.
NSCLC: Pembrolizumab 10 mg/kg Q3W (Part E-Not Enrolled)	Experimental	Biological: PembrolizumabParticipants were to receive pembrolizumab IV at a dose of 10 mg/kg Q3W. No participants were enrolled in this arm.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

In Part A: Histological or cytological diagnosis of MEL or any type of carcinoma, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. In Parts B and D of the study, histological or cytological diagnoses of metastatic MEL with progressive locally advanced or metastatic disease. In Parts C and F, histological or cytological diagnosis of NSCLC. In Part F1, participants with Stage IV NSCLC without prior systemic therapy may be eligible.
Failure of established standard medical anti-cancer therapies for a given tumor type or intolerance to such therapy.
In Parts B, C, D, or F of the study, MEL or NSCLC must be measurable by imaging.
In Part F of the study, NSCLC with PD-L1 gene expression.
Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

Key exclusion criteria (16 listed)

Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the adverse events caused by therapy administered more than 4 weeks prior to first dose.
Participation in a study of an investigational agent or using an investigational device within 30 days of administration of pembrolizumab, with the exception of participants in the follow-up phase.
Other form(s) of antineoplastic therapy anticipated during the period of the study.
History of non-infectious pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease.
Medical condition that requires chronic systemic steroid therapy, or on any other form of immunosuppressive medication, excepting use of inhaled steroids.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PembrolizumabAlso: MK-3475, KEYTRUDA®IV infusion over 30 minutes on Day 1 of each cycle, administered according to dose selection or randomization.	Biological	MEL: Pembrolizumab 10 mg/kg Q2W (Part B), MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D), MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D), NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F), NSCLC: Pembrolizumab 10 mg/kg Q3W (Part E-Not Enrolled), NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F), NSCLC: Pembrolizumab 2 mg/kg Q3W (Part E-Not Enrolled), NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F), NSCLC: Pembrolizumab 5 mg/kg Q3W (Part E-Not Enrolled), Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A), Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1), Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A), Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2), Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2), Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2)

Primary outcome

Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) in Participants With Solid Tumors (Parts A and A1)
Time frame: Up to 28 days in Cycle 1
DLTs were assessed according to NCI-CTCAE v.4.0 during the first cycle (28 days) and were defined as occurrence of any of the following toxicities if judged by the investigator to be possibly, probably or definitely related to study drug administration: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥14 days; Gr 3 nonhematologic toxicity lasting >3 days despite optimal supportive care; any Grade 3 non-hematologic laboratory value if medical intervention was required to treat the participant, the abnormality led to hospitalization, or the abnormality persisted for >1 week; Gr 3 or 4 febrile neutropenia; thrombocytopenia <25,000 cells/mm^3 (if associated with a bleeding event requiring an elective platelet transfusion, or a life-threatening bleeding event which resulted in urgent intervention and admission to an Intensive Care Unit); or Gr 5 toxicity. The number of participants in Part A and Part A1 with a DLT were reported by pembrolizumab dose received.
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced an AE was reported for each arm.
Overall Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Integrated Radiology and Oncology (IRO): Melanoma Participants (Parts B Plus D)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRO was reported as the ORR for each melanoma dose arm (Parts B plus D).
ORR According to RECIST 1.1 as Assessed by Independent Review Committee (IRC): Non-Small Cell Lung Cancer (NSCLC) Participants (Parts C Plus F)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
ORR was defined as the percentage of participants in the analysis population who had a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRC was reported as the ORR for each NSCLC dose arm (Parts C plus F).

28 secondary outcomes

ORR According to Immune-related Response Criteria (irRC) as Assessed by Investigator in Melanoma Participants (Parts B Plus D)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
ORR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Day 28 (AUC 0-28) in Solid Tumor Participants (Parts A and A1)
Time frame: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Infinity (AUC 0-inf) in Solid Tumor Participants (Parts A and A1)
Time frame: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Maximum Concentration (Cmax) of Pembrolizumab in Solid Tumor Participants (Parts A and A1)
Time frame: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Time to Maximum Concentration (Tmax) of Pembrolizumab in Solid Tumor Participants (Parts A and A1)
Time frame: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Terminal Half-Life (t ½) of Pembrolizumab in Solid Tumor Participants (Parts A and A1)
Time frame: Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days)
Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Day 21 (AUC 0-21) in Solid Tumor Participants (Part A2)
Time frame: Cycle 1: Day 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours; Day 5, Day 8: pre- and post-dose; Day 15 (Cycle = 21 days)
Area Under the Concentration-Time Curve of Pembrolizumab From Day 21 to Day 42 (AUC21-42) in Solid Tumor Participants (Part A2)
Time frame: Cycle 1: Day 21; Cycle 2: Day 1: Pre-dose, post-dose at 0.5 and 24 hours, Day 3, Day 8, Day 15 (Cycle = 21 days)
Lowest Plasma Concentration (Ctrough) of Pembrolizumab in Solid Tumor Participants (Parts A, A1, and A2)
Time frame: Parts A and A1: pre-dose at Cycles 2, 4, 6, 8, 10, 12, 14 (cycle=14 days); A2 Cohorts: pre-dose at Cycles 2, 3, 5, 7, 9, 11 (cycle=21 days)
Ctrough of Pembrolizumab in Melanoma Participants (Parts B and D)
Time frame: Part B arms treated every 3 weeks: pre-dose at Cycles 2,5,9,13,17,25,33 (cycle=21 days); Part B treated every 2 weeks: pre-dose at Cycles 2,3,7,13,19,25,31,37 (cycle=14 days); Part D: pre-dose at Cycles 2,3,6,8,12,16,24,32 (cycle=21 days)
Ctrough of Pembrolizumab in NSCLC Participants (Parts C and F)
Time frame: Part C: pre-dose at Cycles 2,5,9,13,17,21 (cycle=21 days); Part F treated every 3 weeks: pre-dose at Cycles 2,3,6,8,12,14,16,24,32 (cycle=21 days); Part F treated every 2 weeks: pre-dose at Cycles 2,3,6,7,8,9,12,16,18,24,32,36,40,48 (cycle=14 days)
Maximum Change From Baseline (CFB) in Tumor Size Assessed by IRC Per RECIST 1.1 According to Programmed Death-Ligand 1 (PD-L1) Immunohistochemical (IHC) Expression Status in Ipilimumab (Ipi)-Exposed and Ipi-Naive Melanoma Participants (Parts B Plus D)
Time frame: Baseline, last available tumor assessment (up to approximately 53 months through Interim Database cut-off date of 18-Sep-2015)
Maximum Change From Baseline (CFB) in Tumor Size Assessed by IRC Per RECIST 1.1 According to PD-L1 IHC Expression Status in Prior Treatment (TRT)-Naïve and Previously-Treated NSCLC Participants (Parts C Plus F)
Time frame: Baseline, last available tumor assessment (up to approximately 53 months through Interim Database cut-off date of 18-Sep-2015)
Disease Control Rate (DCR) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B and D)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
Duration of Response (DOR) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B and D)
Time frame: From time of first documented evidence of CR or PR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months)
Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B Plus D)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
Overall Survival (OS) in Melanoma Participants (Parts B Plus D)
Time frame: Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018)
DCR According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
DOR According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D)
Time frame: From time of first documented evidence of iCR or iPR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months)
PFS According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
DCR According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
DOR According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F)
Time frame: From time of first documented evidence of CR or PR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months)
PFS According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
OS in NSCLC Participants (Parts C Plus F)
Time frame: Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018)
DCR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)
DOR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F)
Time frame: From time of first documented evidence of iCR or iPR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months)
PFS According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F)
Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015)

Results and safety

Results posted to the registry on 13 Dec 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A)	4	0
Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A)	3	0
Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1)	12	0
Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2)	4	0
Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2)	3	1
Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2)	6	0
MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D)	164	18
MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D)	321	24
MEL: Pembrolizumab 10 mg/kg Q2W (Part B)	183	14
NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F)	61	6
NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F)	296	20
NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F)	203	17
NSCLC: Pembrolizumab 2 mg/kg Q3W (Part E-Not Enrolled)	0	0
NSCLC: Pembrolizumab 5 mg/kg Q3W (Part E-Not Enrolled)	0	0
NSCLC: Pembrolizumab 10 mg/kg Q3W (Part E-Not Enrolled)	0	0

Primary outcome: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) in Participants With Solid Tumors (Parts A and A1)

Time frame: Up to 28 days in Cycle 1. Number. Unit: Participants

Measure	Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A) n = 4	Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A) n = 3	Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1) n = 10	Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2) n = 0	Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2) n = 0	Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2) n = 0	MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D) n = 0	MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D) n = 0	MEL: Pembrolizumab 10 mg/kg Q2W (Part B) n = 0	NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F) n = 0	NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F) n = 0	NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F) n = 0
Value	0	0	0	–	–	–	–	–	–	–	–	–

Population analysed: All participants in Parts A and A1 who received ≥1 dose of study treatment and either 1) had a DLT in Cycle 1 or 2) received ≥90% of the prescribed dose of pembrolizumab in Cycle 1 and completed all safety evaluations ≥28 days after the first administration of pembrolizumab without experiencing DLT. Per protocol, Parts A2 and B-F were not analyzed.

Primary outcome: Number of Participants Who Experienced an Adverse Event (AE)

Time frame: Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018). Number. Unit: Participants

Measure	Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A) n = 4	Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A) n = 3	Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1) n = 10	Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2) n = 4	Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2) n = 3	Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2) n = 6	MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D) n = 162	MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D) n = 313	MEL: Pembrolizumab 10 mg/kg Q2W (Part B) n = 180	NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F) n = 61	NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F) n = 287	NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F) n = 202
Value	4	3	9	4	3	6	161	308	178	60	277	198

Population analysed: All participants who received at least 1 dose of study treatment.

Primary outcome: Overall Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Integrated Radiology and Oncology (IRO): Melanoma Participants (Parts B Plus D)

Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015). Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A) n = 0	Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A) n = 0	Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1) n = 0	Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2) n = 0	Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2) n = 0	Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2) n = 0	MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D) n = 162	MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D) n = 313	MEL: Pembrolizumab 10 mg/kg Q2W (Part B) n = 180	NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F) n = 0	NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F) n = 0	NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F) n = 0
Value	–	–	–	–	–	–	30.2 (23.3 to 37.9)	29.4 (24.4 to 34.8)	36.7 (29.6 to 44.2)	–	–	–

Population analysed: All melanoma (Parts B plus D) participants that received ≥1 dose of study treatment. Per protocol, Part A (dose-escalation) was not analyzed for efficacy. NSCLC (Parts C plus F) participants were analyzed and presented separately and are not included in this analysis.

Primary outcome: ORR According to RECIST 1.1 as Assessed by Independent Review Committee (IRC): Non-Small Cell Lung Cancer (NSCLC) Participants (Parts C Plus F)

Time frame: Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015). Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A) n = 0	Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A) n = 0	Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1) n = 0	Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2) n = 0	Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2) n = 0	Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2) n = 0	MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D) n = 0	MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D) n = 0	MEL: Pembrolizumab 10 mg/kg Q2W (Part B) n = 0	NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F) n = 61	NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F) n = 287	NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F) n = 202
Value	–	–	–	–	–	–	–	–	–	19.7 (10.6 to 31.8)	21.6 (17.0 to 26.8)	19.3 (14.1 to 25.4)

Population analysed: All NSCLC (Parts C plus F) participants that received ≥1 dose of study treatment. Per protocol, Part A (dose-escalation) was not analyzed for efficacy. Melanoma (Parts B plus D) participants were analyzed and presented separately and are not included in this analysis.

28 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Solid Tumors: Pembrolizumab 1 mg/kg Q2W (Part A)	1 of 4 (25%)	4 of 4 (100%)	2 of 4
Solid Tumors: Pembrolizumab 3 mg/kg Q2W (Part A)	1 of 3 (33.3%)	3 of 3 (100%)	1 of 3
Solid Tumors: Pembrolizumab 10 mg/kg Q2W (Parts A+A1)	3 of 10 (30%)	8 of 10 (80%)	6 of 12
Solid Tumors: Pembrolizumab Titration Cohort 1 Q3W (Part A2)	0 of 4 (0%)	4 of 4 (100%)	2 of 4
Solid Tumors: Pembrolizumab Titration Cohort 2 Q3W (Part A2)	2 of 3 (66.7%)	3 of 3 (100%)	1 of 3
Solid Tumors: Pembrolizumab Titration Cohort 3 Q3W (Part A2)	2 of 6 (33.3%)	5 of 6 (83.3%)	5 of 6
MEL: Pembrolizumab 2 mg/kg Q3W (Parts B+D)	69 of 162 (42.6%)	158 of 162 (97.5%)	111 of 164
MEL: Pembrolizumab 10 mg/kg Q3W (Parts B+D)	129 of 313 (41.2%)	303 of 313 (96.8%)	213 of 321
MEL: Pembrolizumab 10 mg/kg Q2W (Part B)	79 of 180 (43.9%)	175 of 180 (97.2%)	110 of 183
NSCLC: Pembrolizumab 2 mg/kg Q3W (Part F)	34 of 61 (55.7%)	55 of 61 (90.2%)	52 of 61
NSCLC: Pembrolizumab 10 mg/kg Q3W (Parts C+F)	119 of 287 (41.5%)	271 of 287 (94.4%)	240 of 296
NSCLC: Pembrolizumab 10 mg/kg Q2W (Part F)	86 of 202 (42.6%)	191 of 202 (94.6%)	166 of 203

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25034862Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC, Patnaik A, Dronca R, Zarour H, Joseph RW, Boasberg P, Chmielowski B, Mateus C, Postow MA, Gergich K, Elassaiss-Schaap J, Li XN, Iannone R, Ebbinghaus SW, Kang SP, Daud A. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014 Sep 20;384(9948):1109-17. doi: 10.1016/S0140-6736(14)60958-2. Epub 2014 Jul 15.
Results publication: PubMed 25977344Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, Drengler R, Chen C, Smith L, Espino G, Gergich K, Delgado L, Daud A, Lindia JA, Li XN, Pierce RH, Yearley JH, Wu D, Laterza O, Lehnert M, Iannone R, Tolcher AW. Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors. Clin Cancer Res. 2015 Oct 1;21(19):4286-93. doi: 10.1158/1078-0432.CCR-14-2607. Epub 2015 May 14.
Results publication: PubMed 27117531Chatterjee M, Turner DC, Felip E, Lena H, Cappuzzo F, Horn L, Garon EB, Hui R, Arkenau HT, Gubens MA, Hellmann MD, Dong D, Li C, Mayawala K, Freshwater T, Ahamadi M, Stone J, Lubiniecki GM, Zhang J, Im E, De Alwis DP, Kondic AG, Flotten O. Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Ann Oncol. 2016 Jul;27(7):1291-8. doi: 10.1093/annonc/mdw174. Epub 2016 Apr 26.
Derived from this study: PubMed 37699333Topp BG, Channavazzala M, Mayawala K, De Alwis DP, Rubin E, Snyder A, Wolchok JD, Ribas A. Tumor dynamics in patients with solid tumors treated with pembrolizumab beyond disease progression. Cancer Cell. 2023 Sep 11;41(9):1680-1688.e2. doi: 10.1016/j.ccell.2023.08.004.
Derived from this study: PubMed 35101941Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.
Derived from this study: PubMed 34571336Hamid O, Robert C, Daud A, Carlino MS, Mitchell TC, Hersey P, Schachter J, Long GV, Hodi FS, Wolchok JD, Arance A, Grob JJ, Joshua AM, Weber JS, Mortier L, Jensen E, Diede SJ, Moreno BH, Ribas A. Long-term outcomes in patients with advanced melanoma who had initial stable disease with pembrolizumab in KEYNOTE-001 and KEYNOTE-006. Eur J Cancer. 2021 Nov;157:391-402. doi: 10.1016/j.ejca.2021.08.013. Epub 2021 Sep 25.
Derived from this study: PubMed 33360855Robert C, Hwu WJ, Hamid O, Ribas A, Weber JS, Daud AI, Hodi FS, Wolchok JD, Mitchell TC, Hersey P, Dronca R, Joseph RW, Boutros C, Min L, Long GV, Schachter J, Puzanov I, Dummer R, Lin J, Ibrahim N, Diede SJ, Carlino MS, Joshua AM. Long-term safety of pembrolizumab monotherapy and relationship with clinical outcome: A landmark analysis in patients with advanced melanoma. Eur J Cancer. 2021 Feb;144:182-191. doi: 10.1016/j.ejca.2020.11.010. Epub 2020 Dec 24.
Derived from this study: PubMed 32305010Lala M, Li TR, de Alwis DP, Sinha V, Mayawala K, Yamamoto N, Siu LL, Chartash E, Aboshady H, Jain L. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020 May;131:68-75. doi: 10.1016/j.ejca.2020.02.016. Epub 2020 Apr 15.
Derived from this study: PubMed 31395089van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.
Derived from this study: PubMed 31154919Garon EB, Hellmann MD, Rizvi NA, Carcereny E, Leighl NB, Ahn MJ, Eder JP, Balmanoukian AS, Aggarwal C, Horn L, Patnaik A, Gubens M, Ramalingam SS, Felip E, Goldman JW, Scalzo C, Jensen E, Kush DA, Hui R. Five-Year Overall Survival for Patients With Advanced Non-Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. J Clin Oncol. 2019 Oct 1;37(28):2518-2527. doi: 10.1200/JCO.19.00934. Epub 2019 Jun 2.
Derived from this study: PubMed 30876831Leighl NB, Hellmann MD, Hui R, Carcereny E, Felip E, Ahn MJ, Eder JP, Balmanoukian AS, Aggarwal C, Horn L, Patnaik A, Gubens M, Ramalingam SS, Lubiniecki GM, Zhang J, Piperdi B, Garon EB. Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. Lancet Respir Med. 2019 Apr;7(4):347-357. doi: 10.1016/S2213-2600(18)30500-9. Epub 2019 Mar 12.
Derived from this study: PubMed 30736858Wang M, Chen C, Jemielita T, Anderson J, Li XN, Hu C, Kang SP, Ibrahim N, Ebbinghaus S. Are tumor size changes predictive of survival for checkpoint blockade based immunotherapy in metastatic melanoma? J Immunother Cancer. 2019 Feb 8;7(1):39. doi: 10.1186/s40425-019-0513-4.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab in people with Cancer, Solid Tumor, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) in Participants With Solid Tumors (Parts A and A1) (time frame: Up to 28 days in Cycle 1). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01295827, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2019.