NeoplasmsPhase 1NCT02315066
Study Of OX40 Agonist PF-04518600 Alone And In Combination With 4-1BB Agonist PF-05082566
A Phase 1 study testing PF-04518600 and PF-04518600 plus PF-05082566 in people with Neoplasms, run by Pfizer at 30 sites in 4 countries.
Trial summary
To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- PF-04518600 and PF-04518600 plus PF-05082566
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 174 participants
- Where
- 30 sitesin 4 countries
- Study dates
- 23 Apr 2015to 12 Nov 2020
- 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
- Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
- Part A2 only: Patients with histological or cytological diagnosis of advanced/metastatic HCC who are treatment naïve and have declined standard of care, or have had at least 1 prior line of systemic therapy. Prior anti PD L1/PD 1 therapy is allowed.
- Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
- Part B2
- Arm 1 only:
- Ocular melanoma patients with advanced/metastatic disease, or
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- Cutaneous/acral melanoma patients with advanced/metastatic disease who have received checkpoint inhibitor (anti PD L1, anti PD 1, or anti CTLA4) based treatment on which disease progressed. [Note: Checkpoint inhibitor may have been part of a combination therapy, as long as the combination did not contain OX40 or 4 1BB agonist.] Any questions on prior treatment may be discussed with the Sponsor.
- Arm 2 only:
- Histological or cytological diagnosis of NSCLC with advanced/metastatic disease. Patients must have previously received prior anti PD L1 or anti PD 1 mAb on which disease progressed. [Note: Previous anti PD L1 or anti PD 1 mAb may have been part of a combination therapy, eg, in combination with chemotherapy, as long as the combination did not contain OX40 or 4 1BB agonist.]
- Performance Status of 0 or 1 - Adequate bone marrow, kidney and liver function
Who cannot join
- Brain metastases requiring steroids
- Major surgery, Radiation therapy within 4 weeks of starting study treatment (except: palliative radiotherapy to a limited field is allowed after consultation with sponsor's medical monitor at any time during study participation, including during screening), or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas)
- Active and clinically significant bacterial, fungal, or viral infection
- History of active autoimmune disorders
- History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy
- Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)
- Prior anthracycline treatment and at risk of cardiac failure (New York Heart Association Class 2)
Trial locations and contacts
30 sites in 4 countries.
30 sites in 4 countries
United States24 sites
Massachusetts General Hospital (MGH)
Boston, Massachusetts, 02114
Brigham & Women's Hospital (BWH)
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center (BIDMC)
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute (DFCI)
Boston, Massachusetts, 02215
Massachusetts General/Chelsea HealthCare Center
Chelsea, Massachusetts, 02150
Mass General/North Shore Center for Outpatient Care
Danvers, Massachusetts, 01923
UConn Health, Pharmacy
Farmington, Connecticut, 06030-2205
UConn Health, Neag Comprehensive Cancer Center
Farmington, Connecticut, 06030
Methodist Hospital-Pathology
Houston, Texas, 77030
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
The Angeles Clinic And Research Institute, A Cedars-Sinai Affiliate
Los Angeles, California, 90025
Keck Hospital of USC
Los Angeles, California, 90033
LAC+USC Medical Center
Los Angeles, California, 90033
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Ronald Regan Medical Center
Los Angeles, California, 90095
UCLA Hematology & Oncology Clinic
Los Angeles, California, 90095
Columbia University Medical Center - Herbert Irving Pavilion
New York, New York, 10032
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
Medical Imaging Center of Southern California, Inc.
Santa Monica, California, 90403
Santa Monica UCLA Hematology & Oncology Clinic
Santa Monica, California, 90404
Seattle Cancer Care Alliance
Seattle, Washington, 98109
University of Washington Medical Center
Seattle, Washington, 98195
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
Mass General West
Waltham, Massachusetts, 02451
Netherlands3 sites
The Netherlands Cancer Institute
Amsterdam, 1066 CX
Slotervaart Hospital/Antoni van Leeuwenhoek
Amsterdam, 1066 EC
Erasmus MC
Rotterdam, 3015 GD
France2 sites
Groupe hospitalier Pitie Salpetriere
Paris, 75013
Institut Gustave Roussy
Villejuif, 94805
About this study
Official title: A PHASE 1, OPEN-LABEL, DOSE ESCALATION STUDY OF PF-04518600 AS A SINGLE AGENT AND IN COMBINATION WITH PF-05082566 IN PATIENTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC CANCERS
To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
- Conditions
- Neoplasms
- Being tested
- PF-04518600, PF-04518600 plus PF-05082566
- Keywords
- Immunotherapy, PF-04518600, PF-05082566, solid tumors, tumors, neoplasm metastasis, Phase 1, hepatocellular carcinoma, HCC, liver cancer, ocular melanoma, melanoma, clear cell renal cell carcinoma, RCC, kidney cancer, head and neck squamous cell carcinoma, HNSCC, head and neck cancer, cervical cancer, cancer of the cervix
- Medical subject headings
- Neoplasms, Neoplasm Metastasis, Carcinoma, Hepatocellular, Liver Neoplasms, Uveal Melanoma, Melanoma, Carcinoma, Renal Cell, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-04518600Drug
Part A1 - PF-04518600 will be administered intravenously every 14 days in cohorts of 2 or more patients starting at a dose of 0.01 mg/kg. Increases in dose will continue until MTD is determined
PF-04518600Drug
Part A2 - patients with hepatocellular carcinoma will be randomized to receive treatment with PF-04518600 at various doses administered intravenously
PF-04518600 plus PF-05082566Drug
Part B1 -In cohorts of 2 or more patients, PF-04518600 will be administered intravenously every 2 weeks starting at a dose of 0.1 mg/kg and PF-05082566 will be administered intravenously 4 weeks starting at a dose of 20 mg. Increases in dose will continue until MTD is determined.
PF-04518600 plus PF-05082566Drug
Part B2 - patients with select tumor types (ocular melanoma, cutaneous/acral melanoma or non-small cell lung cancer) will be treated at dose levels based on the OBD selected in Part 1.
| Study group | Role | What they receive |
|---|---|---|
| PF-04518600 | Experimental | OX40 agonist Receives: Drug: PF-04518600 |
| PF-04518600 plus PF-05082566 | Experimental | OX40 (CD134) agonist plus 4-1BB (CD137) agonist Receives: Drug: PF-04518600 plus PF-05082566 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs) in Part A1
DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting >7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported.
Measured: The first 2 cycles of treatment (Day 1 up to Day 28)
Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) and Serious Adverse Event(SAEs), Treatment-Related TEAEs and SAEs in Part A
Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Measured: AEs: The informed consent date up to the last dosing date + 28 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period.
Number of Participants With Laboratory Test Abnormalities in Part A
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick [protein, blood], microscopy [urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells], miscellaneous [urine casts and bacteria]).
Measured: The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable)
Number of Participants With DLTs in Part B1
DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting >7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported.
Measured: The First 2 Cycles of Treatment (Day 1 up to Day 28)
Number of Participants With All-causality TEAEs and SAEs, and Treatment-Related TEAEs and SAEs in Part B
Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Measured: AEs: The informed consent date up to the last dosing date + 60 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period.
Number of Participants With Laboratory Test Abnormalities in Part B
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick [protein, blood], microscopy [urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells], miscellaneous [urine casts and bacteria]).
Measured: The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable)
Secondary outcomes (45)
Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 and Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST) in Part A
ORR was defined as the percentage of patients with best overall response (BOR) of CR or PR relative to the appropriate analysis set.
CR: Complete response is defined (per RECIST 1.1) as disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm.
PR: Partial response is difined (per RECIST 1.1) as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Overall immune related complete response (irCR): Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm.
Overall immune related partial response (irPR): Sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%.
Measured: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median Progression-Free Survival (PFS) in Part A
PFS was defined as the time from randomization date to date of first documentation of progressive disease(PD) based on RECIST, irRECIST or death due to any cause.
PD was progression documented after start date and not qualifying as CR, PR or SD per RECIST.
Measured: Baseline up to 24 months post first dose
Kaplan-Meier Estimate of Median Time to Progression (TTP) in Part A
TTP was defined as the time from start date to the date of the first documentation of PD. PD was documented after start date and not qualifying as CR, PR or SD per RECIST.
Measured: Baseline up to 24 months post first dose
Number of Participants Having Stable Disease (SD) in Part A
SD was defined as persistence of any non target lesions and/or tumor marker level above the normal limits.
Measured: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median Duration of Response (DoR) in Part A
DoR was defined as the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause for patients with an objective response.
CR was defined as complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm) and all target lesions must be assessed.
PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions and all target lesions must be assessed.
Measured: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median Overall Survival (OS) in Part A
OS was defined as time in months from the start of study treatment to date of death due to any cause. OS was calculated as the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 30.44.
Measured: Baseline up to 24 months post first dose.
Overall Survival Rates at Months 6, 12, and 24 in Part A
Probability of survival at 6, 12, and 24 months after the first dose of study treatment.
Measured: Baseline up to 24 months post first dose.
Maximum Serum Concentration (Cmax) of PF-04518600 Following Single Dose on Cycle 1 Day 1 (C1D1) and Steady-State Maximum Serum Concentration(Css,Max) Following Multiple Doses on Cycle 3 Day 1 (C3D1) in Part A
Cmax was defined as maximum observed serum concentration and can be observed directly from data.
Css,max was the Cmax on C3D1.
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A
AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks.
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Area Under the Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A
AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf).
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Terminal Half-Life (t1/2) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A
t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration.
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Lowest Serum Concentration Observed During the Dosing Interval (Cmin) of PF-04518600 Following Multiple Doses on C3D1 in Part A.
Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data.
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Average Serum Concentration Over the Dosing Interval (Cav) of PF-04518600 Following Multiple Doses on C3D1 in Part A
Cav was defined as average serum concentration over the dosing interval.
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Clearance (CL) of PF-04518600 Following Multiple Doses on C3D1 in Part A
Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Apparent Volume of Distribution at Steady State (Vss) of PF-04518600 Following Multiple Doses on C3D1 in Part A.
Vss was defined as volume of distribution at steady state.
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Accumulation Ratio (Rac) of PF-04518600 at C3D1 Following Multiple Doses on C3D1 in Part A
Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1.
Measured: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Number of Participants With Anti Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against PF-04518600 in Part A
ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.
Measured: Baseline up to end of treatment (maximum of 14 weeks).
Mean Unbound Cell Surface OX40 in Part A1
Mean unbound cell surface OX40 in peripheral blood was measured to characterize the degree of target engagement (TE) by PF-04518600 at baseline and multiple doses.
Measured: Pre-dose, 4 and 24 hours post dose on Cycle 1 Day 1, and Day 8 on Cycles 1 to 3, then pre-dose on Cycles 4 and 7 and end of treatment in Part A1
ORR Assessed by RECIST Version 1.1 and irRECIST in Part B
ORR was defined as the percentage of patients with best overall response (BOR) of CR or PR relative to the appropriate analysis set.
CR: Complete response is defined (per RECIST 1.1) as disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm.
PR: Partial response is difined (per RECIST 1.1) as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Overall immune related complete response (irCR): Complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to <10 mm.
Overall immune related partial response (irPR): Sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases ≥30%.
Measured: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median PFS in Part B
PFS was defined as the time from randomization date to date of first documentation of progressive disease(PD) based on RECIST, irRECIST or death due to any cause.
PD was progression documented after start date and not qualifying as CR, PR or SD per RECIST.
Measured: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median TTP in Part B
TTP was defined as the time from start date to the date of the first documentation of PD. PD was documented after start date and not qualifying as CR, PR or SD per RECIST.
Measured: Baseline up to 24 months post first dose.
Number of Participants Having SD in Part B
SD was defined as persistence of any non target lesions and/or tumor marker level above the normal limits.
Measured: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median DoR in Part B
DoR was defined as the time from first documentation of PR or CR to date of first documentation of PD or death due to any cause for patients with an objective response.
CR was defined as complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm) and all target lesions must be assessed.
PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions and all target lesions must be assessed.
Measured: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median OS in Part B
OS was defined as time in weeks or months from the start of study treatment to date of death due to any cause. OS was calculated as the death date or last known alive date (if death date unavailable) minus the date of first dose of study medication plus 1 divided by 7 or 30.44 if in months.
Measured: Baseline up to 24 months post first dose.
Overall Survival Rates at Months 6, 12, and 24 in Part B
Probability of survival at 6, 12, and 24 months after the first dose of study treatment.
Measured: Baseline up to 24 months post first dose.
Cmax of PF-04518600 Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B
Cmax was defined as maximum observed serum concentration and can be observed directly from data.
Css,max was the Cmax on C3D1.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
AUCtau of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
AUCinf of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf).
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
t1/2 of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cmin of PF-04518600 Following Multiple Doses on C3D1 in Part B
Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cav of PF-04518600 Following Multiple Doses on C3D1 in Part B
Cav was defined as average serum concentration over the dosing interval.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
CL of PF-04518600 Following Multiple Doses on C3D1 in Part B
Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Vss of PF-04518600 Following Multiple Doses on C3D1 in Part B
Vss was defined as volume of distribution at steady state.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Rac of PF-04518600 Following Multiple Doses on C3D1 in Part B
Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cmax of Utomilumab Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B
Cmax was defined as maximum observed serum concentration and can be observed directly from data.
Css,max was the Cmax on C3D1.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
AUCtau of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
AUCtau was defined as area under the concentration curve from time 0 to end of dosing interval where dosing interval was 2 weeks.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
AUCinf of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It was obtained from AUC (0-t) plus AUC (t-inf).
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
t1/2 of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
t1/2 was defined as the time measured for the serum concentration to decrease by one half of the initial concentration.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cmin of Utomilumab Following Multiple Doses on C3D1 in Part B
Cmin was defined as Lowest concentration observed during the dosing interval and can be observed directly from data.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cav of Utomilumab Following Multiple Doses on C3D1 in Part B
Cav was defined as average serum concentration over the dosing interval.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
CL of Utomilumab Following Multiple Doses on C3D1 in Part B
Drug clearance was a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL=Dose/AUCss,tau
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Vss of Utomilumab Following Multiple Doses on C3D1 in Part B
Vss was defined as volume of distribution at steady state.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Rac of Utomilumab Following Multiple Doses on C3D1 in Part B
Accumulation ratio was calculated as, Rac obtained from Area Under the Concentration Time Curve (AUC) from Cycle 3 Day 1 divided by AUC from Cycle1 Day 1.
Measured: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Number of Participants With ADA and NAb Against PF-04518600 in Part B
ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.
Measured: Baseline up to end of treatment (maximum of 14 weeks).
Number of Participants With ADA and NAb Against Utomilumab in Part B
ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. nAb never-positive was defined as no positive nAb results at any time point and nAb ever-positive was defined as at least one positive nAb result at any time point.
Measured: Baseline up to end of treatment (maximum of 14 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2014 (estimated)
- Study start23 Apr 2015
- Primary completion12 Nov 2020
- Study completion12 Nov 2020
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 (2)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by PfizerThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02315066
- Sponsor's protocol ID
- B0601002
- Other IDs
- 2014-004107-75, B0601002, OX40, 2014
- Status last verified
- Feb 2022
- First submitted
- 4 Dec 2014
- Last updated
- 21 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Hamid O, Chiappori AA, Thompson JA, Doi T, Hu-Lieskovan S, Eskens FALM, Ros W, Diab A, Spano JP, Rizvi NA, Wasser JS, Angevin E, Ott PA, Forgie A, Yang W, Guo C, Chou J, El-Khoueiry AB. First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors. J Immunother Cancer. 2022 Oct;10(10):e005471. doi: 10.1136/jitc-2022-005471.
PubMed 36302562Diab A, Hamid O, Thompson JA, Ros W, Eskens FALM, Doi T, Hu-Lieskovan S, Klempner SJ, Ganguly B, Fleener C, Wang X, Joh T, Liao K, Salek-Ardakani S, Taylor CT, Chou J, El-Khoueiry AB. A Phase I, Open-Label, Dose-Escalation Study of the OX40 Agonist Ivuxolimab in Patients with Locally Advanced or Metastatic Cancers. Clin Cancer Res. 2022 Jan 1;28(1):71-83. doi: 10.1158/1078-0432.CCR-21-0845. Epub 2021 Oct 6.
PubMed 34615725
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 1, OPEN-LABEL, DOSE ESCALATION STUDY OF PF-04518600 AS A SINGLE AGENT AND IN COMBINATION WITH PF-05082566 IN PATIENTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC CANCERS
- ClinicalTrials.gov ID
- NCT02315066
- Acronym / sponsor ID
- B0601002
- Conditions
- Neoplasms
- Keywords
- Immunotherapy, PF-04518600, PF-05082566, solid tumors, tumors, neoplasm metastasis, Phase 1, hepatocellular carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 174 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 23 Apr 2015 (actual)
- Primary completion
- 12 Nov 2020 (actual)
- Study completion
- 12 Nov 2020 (actual)
- First posted
- 11 Dec 2014 (estimated)
- Results
- Posted 21 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the safety and tolerability at increasing dose levels of PF-04518600 alone or in combination wtih PF-05082566 in patients with select advanced or metastatic carcinoma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PF-04518600 | Experimental | Drug: PF-04518600OX40 agonist |
| PF-04518600 plus PF-05082566 | Experimental | Drug: PF-04518600 plus PF-05082566OX40 (CD134) agonist plus 4-1BB (CD137) agonist |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
- Part A2 only: Patients with histological or cytological diagnosis of advanced/metastatic HCC who are treatment naïve and have declined standard of care, or have had at least 1 prior line of systemic therapy. Prior anti PD L1/PD 1 therapy is allowed.
- Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
- Part B2
- Ocular melanoma patients with advanced/metastatic disease, or
Key exclusion criteria (7 listed)
- Brain metastases requiring steroids
- Major surgery, Radiation therapy within 4 weeks of starting study treatment (except: palliative radiotherapy to a limited field is allowed after consultation with sponsor's medical monitor at any time during study participation, including during screening), or systemic anti-cancer therapy within 4 weeks of study treatment start (6 weeks for mitomycin C or nitrosoureas)
- Active and clinically significant bacterial, fungal, or viral infection
- History of active autoimmune disorders
- History of immune-mediated adverse events requiring immunosuppressive therapy or were grade 3 or higher related to prior immune-modulatory therapy
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 |
|---|---|---|
| PF-04518600Part A1 - PF-04518600 will be administered intravenously every 14 days in cohorts of 2 or more patients starting at a dose of 0.01 mg/kg. Increases in dose will continue until MTD is determined | Drug | PF-04518600 |
| PF-04518600Part A2 - patients with hepatocellular carcinoma will be randomized to receive treatment with PF-04518600 at various doses administered intravenously | Drug | PF-04518600 |
| PF-04518600 plus PF-05082566Part B1 -In cohorts of 2 or more patients, PF-04518600 will be administered intravenously every 2 weeks starting at a dose of 0.1 mg/kg and PF-05082566 will be administered intravenously 4 weeks starting at a dose of 20 mg. Increases in dose will continue until MTD is determined. | Drug | PF-04518600 plus PF-05082566 |
| PF-04518600 plus PF-05082566Part B2 - patients with select tumor types (ocular melanoma, cutaneous/acral melanoma or non-small cell lung cancer) will be treated at dose levels based on the OBD selected in Part 1. | Drug | PF-04518600 plus PF-05082566 |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs) in Part A1
Time frame: The first 2 cycles of treatment (Day 1 up to Day 28)
DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting >7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported.
Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) and Serious Adverse Event(SAEs), Treatment-Related TEAEs and SAEs in Part A
Time frame: AEs: The informed consent date up to the last dosing date + 28 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period.
Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Laboratory Test Abnormalities in Part A
Time frame: The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable)
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick [protein, blood], microscopy [urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells], miscellaneous [urine casts and bacteria]).
Number of Participants With DLTs in Part B1
Time frame: The First 2 Cycles of Treatment (Day 1 up to Day 28)
DLT was defined as any of the following adverse events occurring in the first two cycle of treatment (28 days), unless there was a clear alternative explanation: hematologic: grade 4 neutropenia lasting >7 days, febrile neutropenia; grade ≥3 neutropenic infection; grade ≥3 thrombocytopenia with clinically significant bleeding or requiring medical intervention; grade 4 thrombocytopenia; grade 4 anemia; grade ≥3 anemia related to hemolysis or autoimmune disease. non hematologic: grade ≥3 toxicities that were considered clinically significant, including cytokine release syndrome, infusion reactions and allergic reactions, except those that had not been maximally treated or could be easily treated. The severity of adverse events was graded as per common terminology criteria for adverse events(CTCAE) version 4.03, and there were no DLTs reported.
Number of Participants With All-causality TEAEs and SAEs, and Treatment-Related TEAEs and SAEs in Part B
Time frame: AEs: The informed consent date up to the last dosing date + 60 days or all drug-related toxicities resolved date. SAEs: The informed consent date through first dosing date + 98 days or up to the last dosing date + 60 days, and any post-reporting period.
Adverse event (AE) was graded by the investigator according to CTCAE version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA): Grade 3 (Severe) events=unacceptable or intolerable events. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 (Death) events=death related to an AE. Treatment-emergent events=between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs were defined as those with initial onset or increasing in severity after the first dose of study medication. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Laboratory Test Abnormalities in Part B
Time frame: The first dosing date to the earlier date between the last dosing date + 35 days and the first new anti-cancer therapy date (if applicable)
Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, partial thromboplastin time (PTT), Prothrombin (PT), PT international ratio); liver function (aspartate aminotransferase(AST), alanine aminotransferase(ALT), total bilirubin, gamma-glutamyl transpeptidase(GT), alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium , phosphate, magnesium); clinical chemistry (glucose, creatine kinase, thyroxine (T4), thyroid stimulating hormone(TSH)), Amylase, Lipase), urinalysis (dipstick [protein, blood], microscopy [urine red blood cell (RBC), white blood cell (WBC), Epithelial Cells], miscellaneous [urine casts and bacteria]).
45 secondary outcomes
Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 and Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST) in Part A
Time frame: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median Progression-Free Survival (PFS) in Part A
Time frame: Baseline up to 24 months post first dose
Kaplan-Meier Estimate of Median Time to Progression (TTP) in Part A
Time frame: Baseline up to 24 months post first dose
Number of Participants Having Stable Disease (SD) in Part A
Time frame: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median Duration of Response (DoR) in Part A
Time frame: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median Overall Survival (OS) in Part A
Time frame: Baseline up to 24 months post first dose.
Overall Survival Rates at Months 6, 12, and 24 in Part A
Time frame: Baseline up to 24 months post first dose.
Maximum Serum Concentration (Cmax) of PF-04518600 Following Single Dose on Cycle 1 Day 1 (C1D1) and Steady-State Maximum Serum Concentration(Css,Max) Following Multiple Doses on Cycle 3 Day 1 (C3D1) in Part A
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Area Under the Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Terminal Half-Life (t1/2) of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part A
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Lowest Serum Concentration Observed During the Dosing Interval (Cmin) of PF-04518600 Following Multiple Doses on C3D1 in Part A.
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Average Serum Concentration Over the Dosing Interval (Cav) of PF-04518600 Following Multiple Doses on C3D1 in Part A
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Clearance (CL) of PF-04518600 Following Multiple Doses on C3D1 in Part A
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Apparent Volume of Distribution at Steady State (Vss) of PF-04518600 Following Multiple Doses on C3D1 in Part A.
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Accumulation Ratio (Rac) of PF-04518600 at C3D1 Following Multiple Doses on C3D1 in Part A
Time frame: For Part A1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1, and 4 hours post dose on Day 1 of Cycles 3; For Par A2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Number of Participants With Anti Drug Antibody (ADA) and Neutralizing Antibody (NAb) Against PF-04518600 in Part A
Time frame: Baseline up to end of treatment (maximum of 14 weeks).
Mean Unbound Cell Surface OX40 in Part A1
Time frame: Pre-dose, 4 and 24 hours post dose on Cycle 1 Day 1, and Day 8 on Cycles 1 to 3, then pre-dose on Cycles 4 and 7 and end of treatment in Part A1
ORR Assessed by RECIST Version 1.1 and irRECIST in Part B
Time frame: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median PFS in Part B
Time frame: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median TTP in Part B
Time frame: Baseline up to 24 months post first dose.
Number of Participants Having SD in Part B
Time frame: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median DoR in Part B
Time frame: Baseline up to 24 months post first dose.
Kaplan-Meier Estimate of Median OS in Part B
Time frame: Baseline up to 24 months post first dose.
Overall Survival Rates at Months 6, 12, and 24 in Part B
Time frame: Baseline up to 24 months post first dose.
Cmax of PF-04518600 Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
AUCtau of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
AUCinf of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
t1/2 of PF-04518600 Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cmin of PF-04518600 Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cav of PF-04518600 Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
CL of PF-04518600 Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Vss of PF-04518600 Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Rac of PF-04518600 Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cmax of Utomilumab Following Single Dose on C1D1 and Css,Max Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
AUCtau of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
AUCinf of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
t1/2 of Utomilumab Following Single Dose on C1D1 and Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cmin of Utomilumab Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Cav of Utomilumab Following Multiple Doses on C3D1 in Part B
Time frame: For Part B1, pre-dose, 1, 4, and 24 hours post dose on C1D1, pre-dose, 1 hour post dose on Day 1 of Cycles 3; For Part B2, pre-dose, 1, and 4 hours post dose on C1D1, pre-dose and 1 hour post dose on Day 1 of Cycles 3.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36302562Hamid O, Chiappori AA, Thompson JA, Doi T, Hu-Lieskovan S, Eskens FALM, Ros W, Diab A, Spano JP, Rizvi NA, Wasser JS, Angevin E, Ott PA, Forgie A, Yang W, Guo C, Chou J, El-Khoueiry AB. First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors. J Immunother Cancer. 2022 Oct;10(10):e005471. doi: 10.1136/jitc-2022-005471.
- Derived from this study: PubMed 34615725Diab A, Hamid O, Thompson JA, Ros W, Eskens FALM, Doi T, Hu-Lieskovan S, Klempner SJ, Ganguly B, Fleener C, Wang X, Joh T, Liao K, Salek-Ardakani S, Taylor CT, Chou J, El-Khoueiry AB. A Phase I, Open-Label, Dose-Escalation Study of the OX40 Agonist Ivuxolimab in Patients with Locally Advanced or Metastatic Cancers. Clin Cancer Res. 2022 Jan 1;28(1):71-83. doi: 10.1158/1078-0432.CCR-21-0845. Epub 2021 Oct 6.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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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.
Pfizer CT.gov Call Center study director
Pfizer
30 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PF-04518600 and PF-04518600 plus PF-05082566 in people with Neoplasms, run by Pfizer at 30 sites in 4 countries.
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 10 inclusion and 7 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 21 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Netherlands, France, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
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 21 Apr 2022). 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 With Dose Limiting Toxicities (DLTs) in Part A1 (time frame: The first 2 cycles of treatment (Day 1 up to Day 28)). The study lists 6 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 NCT02315066, which also lists 2 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 21 Apr 2022.