AzTrials
AzTrials

Solid TumorPhase 1NCT01840579

Study of Pembrolizumab (MK-3475) Monotherapy in Advanced Solid Tumors and Pembrolizumab Combination Therapy in Advanced Non-small Cell Lung Cancer/ Extensive-disease Small Cell Lung Cancer (MK-3475-011/KEYNOTE-011)

A Phase 1 study testing Pembrolizumab 2 mg/kg, Pembrolizumab 10 mg/kg and Pembrolizumab 200 mg in people with Solid Tumor and Non-small Cell Lung Cancer, 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

This study using pembrolizumab (MK-3475) will be done in 5 parts. In Part A, successive participant cohorts with advanced solid tumors will receive pembrolizumab to assess the safety and tolerability of monotherapy. Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
Pembrolizumab 2 mg/kg, Pembrolizumab 10 mg/kg and Pembrolizumab 200 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
No sites listed yet
Study dates
26 Apr 2013to 28 Feb 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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In Part A: has a histological or cytological diagnosis of solid tumor, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy
  • In Part B, C, and D: has a histologically- or cytologically-confirmed diagnosis of NSCLC (Stage IIIB/IV) and are naïve to systemic therapy
  • In Part C: has a histologically- or cytologically-confirmed diagnosis of squamous cancer
  • In Part E: has a histologically- or cytologically-confirmed diagnosis of SCLC (ED stage) and are naïve to systemic therapy
  • Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Has adequate organ function
  • Female participants of reproductive potential must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start)
  • Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 120 days after the last dose of study therapy and for up to 180 days after the last dose of chemotherapeutic agents

Who cannot join

  • Has had cancer therapy within 2 weeks (Part E) or 4 weeks (Parts A, B, C, and D) prior to the first dose of study therapy, or not recovered from the adverse events of agents administered more than 4 weeks prior to the first dose of study therapy.
  • Part A: Chemotherapy, radiation therapy, biological therapy or kinase inhibitors
  • Parts B, C, D and E: Radiation therapy
  • For Part B: has a histological diagnosis of squamous cancer
  • Is currently participating or has participated in a study with an investigational agent or using an investigational device within 30 days of first dose of study therapy
  • Is expected to require any other form of antineoplastic therapy while on study
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  • Is on chronic systemic steroid therapy within two weeks prior to the first dose of trial treatment or on any other form of immunosuppressive medication
  • For Part C: Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events version 4 criteria
  • Has interstitial lung disease detected by chest computed tomography (CT), or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary.

About this study

Official title: A Phase I Study of MK-3475 Alone in Subjects With Advanced Solid Tumors and in Combination With Platinum-Doublet Chemotherapy or Immunotherapy in Subjects With Advanced Non-Small Cell Lung Cancer/Extensive-Disease Small Cell Lung Cancer.

This study using pembrolizumab (MK-3475) will be done in 5 parts. In Part A, successive participant cohorts with advanced solid tumors will receive pembrolizumab to assess the safety and tolerability of monotherapy. In Parts B, C, and D, participants with advanced non-small cell lung cancer (NSCLC) will receive pembrolizumab in combination with either cisplatin/pemetrexed or carboplatin/pemetrexed (Part B); with either carboplatin/paclitaxel or carboplatin/nab-paclitaxel (Part C); or with ipilimumab (Part D) by non-random assignment to assess the safety and tolerability of the combination therapy. In Part E, participants with untreated Extensive-disease (ED) Small Cell Lung Cancer (SCLC) will receive pembrolizumab in combination with either cisplatin/etoposide, carboplatin/etoposide, or cisplatin/etoposide with prophylactic use of granulocyte colony-stimulating factor (lasting G-CSF [pegfilgrastim]) by non-random assignment to assess the safety and tolerability of the combination therapy.

Being tested
Pembrolizumab 2 mg/kg, Pembrolizumab 10 mg/kg, Pembrolizumab 200 mg, Cisplatin 75 mg/m^2, Pemetrexed 500 mg/m^2
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma

What participants receive

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

  • Pembrolizumab 2 mg/kgBiological

    Also called KEYTRUDA®

    Administered as an intravenous (IV) infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)

  • Pembrolizumab 10 mg/kgBiological

    Also called KEYTRUDA®

    Administered as an IV infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)

  • Pembrolizumab 200 mgBiological

    Also called KEYTRUDA®

    Administered as an IV infusion on Day 1 of each 21-day cycle

  • Cisplatin 75 mg/m^2Drug

    Administered as an IV infusion on Day 1 of each 21-day cycle

  • Pemetrexed 500 mg/m^2Drug

    Administered as an IV infusion on Day 1 of each 21-day cycle

  • Carboplatin AUC 5 mg/mL/minDrug

    Administered as an IV infusion on Day 1 of each 21-day cycle

  • Carboplatin AUC 6 mg/mL/minDrug

    Administered as an IV infusion on Day 1 of each 21-day cycle

  • Paclitaxel 200 mg/m^2Drug

    Administered as an IV infusion on Day 1 of each 21-day cycle

  • Nab-paclitaxel 100 mg/m^2Drug

    Also called ABRAXANE®

    Administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle

  • Ipilimumab 1 mg/kgBiological

    Also called YERVOY®

    Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days)

  • Etoposide 100 mg/m^2Drug

    Also called TOPOSAR®, VEPESID®, ETOPOPHOS®, EPOSIN®

    Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle

  • G-CSF (pegfilgrastim) 3.6 mgDrug

    Also called Neulasta®

    Administered as a subcutaneous injection on Day 4 of Cycle 1

Study groups in NCT01840579
Study groupRoleWhat they receive
Pembrolizumab 2 mg/kgExperimentalIn Part A, participants receive intravenous (IV) Pembrolizumab 2 mg/kg on Day 1 of Cycle 1 (28 days), Cycle 2 and any additional cycles (14 days).
Receives: Biological: Pembrolizumab 2 mg/kg
Pembrolizumab 10 mg/kgExperimentalIn Part A, participants receive IV Pembrolizumab 10 mg/kg on Day 1 of Cycle 1 (28 days), Cycle 2 and any additional cycles (14 days).
Receives: Biological: Pembrolizumab 10 mg/kg
Pembrolizumab+Cisplatin/PemetrexedExperimentalIn Part B, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m^2 + IV Pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pemetrexed in combination with IV pembrolizumab is permitted per standard of care, followed by IV pembrolizumab 200 mg every 3 weeks.
Receives: Biological: Pembrolizumab 200 mg; Drug: Cisplatin 75 mg/m^2; Drug: Pemetrexed 500 mg/m^2
Pembrolizumab+Carboplatin/PemetrexedExperimentalIn Part B, participants receive IV Pembrolizumab 200 mg + IV Carboplatin Area Under The Curve (AUC) 5 mg/mL/minute + IV Pemetrexed 500 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pemetrexed in combination with IV pembrolizumab is permitted per standard of care, followed by IV pembrolizumab 200 mg every 3 weeks.
Receives: Biological: Pembrolizumab 200 mg; Drug: Pemetrexed 500 mg/m^2; Drug: Carboplatin AUC 5 mg/mL/min
Pembrolizumab+Carboplatin/PaclitaxelExperimentalIn Part C, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 6 mg/mL/minute + IV Paclitaxel 200 mg/m^2 on Day 1 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.
Receives: Biological: Pembrolizumab 200 mg; Drug: Carboplatin AUC 6 mg/mL/min; Drug: Paclitaxel 200 mg/m^2
Pembrolizumab+Carboplatin/Nab-paclitaxelExperimentalIn Part C, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 6 mg/mL/minute on Day 1 of each 21-day cycle + IV Nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.
Receives: Biological: Pembrolizumab 200 mg; Drug: Carboplatin AUC 6 mg/mL/min; Drug: Nab-paclitaxel 100 mg/m^2
Pembrolizumab+IpilimumabExperimentalIn Part D, participants receive IV Pembrolizumab 200 mg on Day 1 of each 21-day cycle + IV Ipilimumab 1 mg/kg on Day 1 of every other 21-day cycle (every 42 days) for a maximum of 18 cycles of Ipilimumab (35 doses of Pembrolizumab).
Receives: Biological: Pembrolizumab 200 mg; Biological: Ipilimumab 1 mg/kg
Pembrolizumab+Cisplatin/EtoposideExperimentalIn Part E, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m^2 on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.
Receives: Biological: Pembrolizumab 200 mg; Drug: Cisplatin 75 mg/m^2; Drug: Etoposide 100 mg/m^2
Pembrolizumab+Carboplatin/EtoposideExperimentalIn Part E, participants receive IV Pembrolizumab 200 mg + IV Carboplatin AUC 5 mg/mL/minute on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.
Receives: Biological: Pembrolizumab 200 mg; Drug: Carboplatin AUC 5 mg/mL/min; Drug: Etoposide 100 mg/m^2
Pembrolizumab+Cisplatin/Etoposide+G-CSFExperimentalIn Part E, participants receive IV Pembrolizumab 200 mg + IV Cisplatin 75 mg/m^2 on Day 1 of each 21-day cycle + IV Etoposide 100 mg/m^2 on Days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles + lasting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) 3.6 mg on Day 4 of Cycle 1. After completion of the initial therapy, maintenance therapy with IV pembrolizumab 200 mg every 3 weeks.
Receives: Biological: Pembrolizumab 200 mg; Drug: Cisplatin 75 mg/m^2; Drug: G-CSF (pegfilgrastim) 3.6 mg

What is being measured

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

  1. Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)

    The following toxicities graded per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0) were considered DLTs if judged by the investigator to be related to either study drug:

    • Grade (G) 4 neutropenia lasting >7 days
    • Grade 3 and Grade 4 febrile neutropenia
    • Grade 4 thrombocytopenia (<25,000/mm^3)
    • Grade 4 anemia
    • Grade 4 non-hematologic toxicity (not laboratory)
    • Grade 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care
    • Any Grade 3 non-hematologic laboratory value if medical intervention is required to treat the participant or the abnormality persists for >7 days.
    • (Part D only) Missing the second dose of pembrolizumab (Cycle1 Day 22) due to drug-related adverse event

    Measured: Cycle 1 (first dose and up to 4 weeks in Part A, 3 weeks in Parts B, C, E, and 6 weeks in Part D)

  2. Number of Participants Who Experienced at Least One Adverse Event (AE)

    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

    Measured: Up to approximately 51.3 months

  3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

    Measured: Up to approximately 37.9 months

Secondary outcomes (39)

  1. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E

    Cmax was the maximum observed concentration of pembrolizumab in serum. For Part A, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), 6 hour (hr) (±30 min), and 24hr; Days 2, 3, 8, 15, and 22 (±2 hr for Day 2 to Day 22) after completion of infusion. For Parts B, C, and E, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), and Day 15 (±24 hr) after completion of infusion. For Part D, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), Day 15, and Day 22 (±24 hr) after completion of infusion. Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Cmax is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for Cmax was planned for Parts A, B, C, D, and E.

    Measured: At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days)

  2. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 2 at pre-dose and 0-30 minutes post-dose. Cycle 2 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 2 was only planned for Part A.

    Measured: Cycle 2 Day 1 pre- and post-dose

  3. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 4 at pre-dose and 0-30 minutes post-dose and for Part D on Day 22 of Cycle 4 at pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and 0-30 minutes post-dose. Cycle 4 length for Part A was 14 days. Cycle 4 length for Part D was 42 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 4 was only planned for Parts A and D.

    Measured: Cycle 4 Day 1 pre- and post-dose (Part A) and Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose (Part D)

  4. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: Part A

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 6 at pre-dose and 0-30 minutes post-dose. Cycle 6 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 6 was only planned for Part A.

    Measured: Cycle 6 Day 1 pre- and post-dose

  5. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Parts A, B, C and E on Day 1 of Cycle 8 at pre-dose and 0-30 minutes post-dose. Cycle 8 length for Part A was 14 days. Cycle 8 length for Parts B, C, and E was 21 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 8 was only planned for Parts A, B, C, and E.

    Measured: Cycle 8 Day 1 pre- and post-dose

  6. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 10 at pre-dose and 0-30 minutes post-dose. Cycle 10 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 10 was only planned for Part A.

    Measured: Cycle 10 Day 1 pre- and post-dose

  7. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 12: Part A

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 12 at pre-dose and 0-30 minutes post-dose. Cycle 12 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 12 was only planned for Part A.

    Measured: Cycle 12 Day 1 pre- and post-dose

  8. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 14: Part A

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 14 at pre-dose and 0-30 minutes post-dose. Cycle 14 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 14 was only planned for Part A.

    Measured: Cycle 14 Day 1 pre- and post-dose

  9. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 16: Part A

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 16 at pre-dose and 0-30 minutes post-dose. Cycle 16 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 16 was only planned for Part A.

    Measured: Cycle 16 Day 1 pre- and post-dose

  10. Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 18: Part A

    Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 18 at pre-dose and 0-30 minutes post-dose. Cycle 18 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 18 was only planned for Part A.

    Measured: Cycle 18 Day 1 pre- and post-dose

  11. Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E

    Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. For Part A, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), 6 hour (hr) (±30 min), and 24hr; Days 2, 3, 8, 15, and 22 (±2 hr for Day 2 to Day 22) after completion of infusion. For Parts B, C, and E, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), and Day 15 (±24 hr) after completion of infusion. For Part D, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), Day 15, and Day 22 (±24 hr) after completion of infusion. Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 1 was planned for Parts A, B, C, D, and E.

    Measured: At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days)

  12. Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 4: Part D

    Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. Blood sampling was taken for Part D on Day 22 of Cycle 4 at pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and 0-30 minutes post-dose. Cycle length for Part D was 42 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 4 was only planned for Part D.

    Measured: Cycle 4 Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose

  13. Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E

    Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 8 at pre-dose and 0-30 minutes post-dose. Cycle 8 for Parts B, C, and E was 21 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 8was planned for Parts B, C, and E.

    Measured: Cycle 8 Day 1 pre- and post-dose

  14. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 1 Ctrough was taken for Parts A, B, C, D, and E on Day 1 of Cycle 2 at pre-dose (prior to Cycle 2 infusion). Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 1 Ctrough was planned for Parts A, B, C, D, and E.

    Measured: Cycle 2 Day 1 pre-dose

  15. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 2: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 2 Ctrough was taken for Part D on Day 22 of Cycle 2 at pre-dose (prior to Cycle 3 infusion). Cycle 2 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 2 Ctrough was only planned for Part D.

    Measured: Cycle 2 Day 22 pre-dose

  16. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 3 Ctrough was taken for Part D on Day 22 of Cycle 3 at pre-dose (prior to Cycle 4 infusion). Cycle 3 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV).

    Measured: Cycle 3 Day 22 pre-dose

  17. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 3 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 4 at pre-dose (prior to Cycle 4 infusion). Cycle 3 length for Part A was 14 days. Cycle 3 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV).

    Measured: Cycle 4 Day 1 at Pre-dose

  18. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 4: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 4 Ctrough was taken for Part D on Day 22 of Cycle 4 at pre-dose (prior to Cycle 5 infusion). Cycle 4 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 4 Ctrough was only planned for Part D.

    Measured: Cycle 4 Day 22 pre-dose

  19. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 5 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 6 at pre-dose (prior to Cycle 6 infusion). Cycle 5 length for Part A was 14 days. Cycle 5 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 5 Ctrough was only planned for Parts A, B, C, and E.

    Measured: Cycle 6 Day 1 pre-dose

  20. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 6: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 6 Ctrough was taken for Part D on Day 22 of Cycle 6 at pre-dose (prior to Cycle 7 infusion). Cycle 6 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 6 Ctrough was only planned for Part D.

    Measured: Cycle 6 Day 22 pre-dose

  21. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 7 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 8 at pre-dose (prior to Cycle 8 infusion). Cycle 7 length for Part A was 14 days. Cycle 7 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 7 Ctrough was only planned for Parts A, B, C, and E.

    Measured: Cycle 8 Day 1 pre-dose

  22. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 8: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 8 Ctrough was taken for Part D on Day 22 of Cycle 8 at pre-dose (prior to Cycle 9 infusion). Cycle 8 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 8 Ctrough was only planned for Part D.

    Measured: Cycle 8 Day 22 pre-dose

  23. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 9 Ctrough was taken for Part A on Day 1 of Cycle 10 at pre-dose (prior to Cycle 10 infusion). Cycle 9 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 9 Ctrough was only planned for Part A.

    Measured: Cycle 10 Day 1 pre-dose

  24. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 10: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 10 Ctrough was taken for Part D on Day 22 of Cycle 10 at pre-dose (prior to Cycle 11 infusion). Cycle 10 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 10 Ctrough was only planned for Part D.

    Measured: Cycle 10 Day 22 pre-dose

  25. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 11 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 12 at pre-dose (prior to Cycle 12 infusion). Cycle 11 length for Part A was 14 days. Cycle 11 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 11 Ctrough was only planned for Parts A, B, C, and E.

    Measured: Cycle 12 Day 1 Pre-dose

  26. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 12: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 12 Ctrough was taken for Part D on Day 22 of Cycle 12 at pre-dose (prior to Cycle 13 infusion). Cycle 12 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 12 Ctrough was only planned for Part D.

    Measured: Cycle 12 Day 22 pre-dose

  27. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 13: Part A

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 13 Ctrough was taken for Part A on Day 1 of Cycle 14 at pre-dose (prior to Cycle 14 infusion). Cycle 13 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 13 Ctrough was only planned for Part A.

    Measured: Cycle 14 Day 1 pre-dose

  28. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 14: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 14 Ctrough was taken for Part D on Day 22 of Cycle 14 at pre-dose (prior to Cycle 15 infusion). Cycle 14 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 14 Ctrough was only planned for Part D.

    Measured: Cycle 14 Day 22 pre-dose

  29. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts A, B, C, and E on Day 1 of Cycle 16 at pre-dose (prior to Cycle 16 infusion). Cycle 15 length for Part A was 14 days. Cycle 15 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 15 Ctrough was only planned for Parts A, B, C, and E.

    Measured: Cycle 16 Day 1 pre-dose

  30. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 16: Part D

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 16 Ctrough was taken for Part D on Day 22 of Cycle 16 at pre-dose (prior to Cycle 17 infusion). Cycle 16 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 16 Ctrough was only planned for Part D.

    Measured: Cycle 16 Day 22 pre-dose

  31. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 17: Part A

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Part A on Day 1 of Cycle 18 at pre-dose (prior to Cycle 18 infusion). Cycle 17 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 17 Ctrough was planned for Part A.

    Measured: Cycle 18 Day 1 pre-dose

  32. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 20 at pre-dose (prior to Cycle 20 infusion). Cycle 19 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 19 Ctrough was only planned for Parts B, C, and E.

    Measured: Cycle 20 Day 1 Pre-dose

  33. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 24 at pre-dose (prior to Cycle 24 infusion). Cycle 23 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 23 Ctrough was only planned for Parts B, C, and E.

    Measured: Cycle 24 Day 1 Pre-dose

  34. Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E

    Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 28 at pre-dose (prior to Cycle 28 infusion). Cycle 27 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 27 Ctrough was only planned for Parts B, C, and E.

    Measured: Cycle 28 Day 1 Pre-dose

  35. Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1

    AUC 0-28 was the AUC of pembrolizumab from time zero to 28 days after dosing. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 pre-dose. Cycle 1 length was 28 days. AUC 0-28 is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for AUC 0-28 was only planned for Part A Cycle 1.

    Measured: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

  36. Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1

    AUC 0-inf was the AUC of pembrolizumab from time zero to infinity after dosing. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 pre-dose. Cycle 1 length was 28 days. AUC 0-inf is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for AUC 0-inf was only planned for Part A Cycle 1.

    Measured: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

  37. Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1

    t1/2 was the time required to divide the pembrolizumab concentration by two after reaching pseudo-equilibrium. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and pre-dose Day 1 of the following cycle prior to pembrolizumab infusion. Cycle 1 length A was 28 days. t1/2 is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for t1/2 was only planned for Part A Cycle 1.

    Measured: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

  38. Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1

    Vz was the volume of distribution during the terminal phase. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 prior to pembrolizumab infusion. Cycle 1 length A was 28 days. Vz is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for Vz was only planned for Part A Cycle 1.

    Measured: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

  39. Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1

    CL was the volume of plasma from which pembrolizumab was eliminated per unit time. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 prior to pembrolizumab infusion. Cycle 1 length A was 28 days. CL is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for CL was only planned for Part A Cycle 1.

    Measured: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

Timeline

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

  1. First posted25 Apr 2013 (estimated)
  2. Study start26 Apr 2013
  3. Primary completion28 Feb 2020
  4. Study completion28 Feb 2020

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01840579
Sponsor's protocol ID
3475-011
Other IDs
132249, MK-3475-011, KEYNOTE-011
Status last verified
May 2021
First submitted
23 Apr 2013
Last updated
22 Jun 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Shimizu T, Seto T, Hirai F, Takenoyama M, Nosaki K, Tsurutani J, Kaneda H, Iwasa T, Kawakami H, Noguchi K, Shimamoto T, Nakagawa K. Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors. Invest New Drugs. 2016 Jun;34(3):347-54. doi: 10.1007/s10637-016-0347-6. Epub 2016 Mar 22.

    PubMed 27000274

  • Nogami N, Umemura S, Kozuki T, Zenke Y, Ohtani J, Ishii M, Han S, Noguchi K, Horinouchi H. A phase 1 study of pembrolizumab plus ipilimumab as first-line treatment in Japanese patients with advanced non-small-cell lung cancer. Respir Investig. 2025 May;63(3):296-302. doi: 10.1016/j.resinv.2025.02.010. Epub 2025 Mar 3.

    PubMed 40036983

  • Nogami N, Tokito T, Zenke Y, Satouchi M, Seto T, Saka H, Ohtani J, Han S, Noguchi K, Nishio M. Phase 1 study of pembrolizumab plus chemotherapy in Japanese patients with extensive-stage small-cell lung cancer. Invest New Drugs. 2024 Feb;42(1):136-144. doi: 10.1007/s10637-023-01411-1. Epub 2024 Feb 1.

    PubMed 38300341

  • Kurata T, Nakagawa K, Satouchi M, Seto T, Sawada T, Han S, Homma M, Noguchi K, Nogami N. Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC. Cancer Treat Res Commun. 2021;29:100458. doi: 10.1016/j.ctarc.2021.100458. Epub 2021 Sep 15.

    PubMed 34607222

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab 2 mg/kg, Pembrolizumab 10 mg/kg and Pembrolizumab 200 mg in people with Solid Tumor and Non-small Cell Lung Cancer, 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 8 inclusion and 9 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 22 Jun 2021. 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 22 Mar 2021). 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 Who Experienced Dose-limiting Toxicities (DLTs) (time frame: Cycle 1 (first dose and up to 4 weeks in Part A, 3 weeks in Parts B, C, E, and 6 weeks in Part D)). The study lists 3 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 NCT01840579, which also lists 4 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 22 Jun 2021.

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