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)

Sponsor
Merck Sharp & Dohme LLC
Study ID
NCT01840579
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
20 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pembrolizumab 2 mg/kg — BIOLOGICAL
    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/kg — BIOLOGICAL
    Administered as an IV infusion on Day 1 of Cycle 1 (28 days), Cycle 2 (14 days), and Cycle 3 (14 days)
  • Pembrolizumab 200 mg — BIOLOGICAL
    Administered as an IV infusion on Day 1 of each 21-day cycle
  • Cisplatin 75 mg/m^2 — DRUG
    Administered as an IV infusion on Day 1 of each 21-day cycle
  • Pemetrexed 500 mg/m^2 — DRUG
    Administered as an IV infusion on Day 1 of each 21-day cycle
  • Carboplatin AUC 5 mg/mL/min — DRUG
    Administered as an IV infusion on Day 1 of each 21-day cycle
  • Carboplatin AUC 6 mg/mL/min — DRUG
    Administered as an IV infusion on Day 1 of each 21-day cycle
  • Paclitaxel 200 mg/m^2 — DRUG
    Administered as an IV infusion on Day 1 of each 21-day cycle
  • Nab-paclitaxel 100 mg/m^2 — DRUG
    Administered as an IV infusion on Days 1, 8, and 15 of each 21-day cycle
  • Ipilimumab 1 mg/kg — BIOLOGICAL
    Administered as an IV infusion on Day 1 of every other 21-day cycle (every 42 days)
  • Etoposide 100 mg/m^2 — DRUG
    Administered as an IV infusion on Days 1, 2, and 3 of each 21-day cycle
  • G-CSF (pegfilgrastim) 3.6 mg — DRUG
    Administered as a subcutaneous injection on Day 4 of Cycle 1

Study Details

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.

Key Dates

Start date
Apr 26, 2013
Status verified
May 2021
Primary completion
Feb 28, 2020
Completion
Feb 28, 2020

Study Design

Enrollment
57 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Pembrolizumab 2 mg/kg
    In 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).
  • Experimental: Pembrolizumab 10 mg/kg
    In 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).
  • Experimental: Pembrolizumab+Cisplatin/Pemetrexed
    In 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.
  • Experimental: Pembrolizumab+Carboplatin/Pemetrexed
    In 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.
  • Experimental: Pembrolizumab+Carboplatin/Paclitaxel
    In 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.
  • Experimental: Pembrolizumab+Carboplatin/Nab-paclitaxel
    In 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.
  • Experimental: Pembrolizumab+Ipilimumab
    In 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).
  • Experimental: Pembrolizumab+Cisplatin/Etoposide
    In 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.
  • Experimental: Pembrolizumab+Carboplatin/Etoposide
    In 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.
  • Experimental: Pembrolizumab+Cisplatin/Etoposide+G-CSF
    In 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.

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) ]

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