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)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Solid Tumor; Small Cell Lung Cancer; Non-small Cell Lung Cancer

Treatments: Drug: Carboplatin AUC 6 mg/mL/min; Drug: Pemetrexed 500 mg/m^2; Biological: Ipilimumab 1 mg/kg; Biological: Pembrolizumab 2 mg/kg; Drug: Paclitaxel 200 mg/m^2; Drug: Etoposide 100 mg/m^2; Drug: Nab-paclitaxel 100 mg/m^2; Drug: G-CSF (pegfilgrastim) 3.6 mg; Drug: Cisplatin 75 mg/m^2; Biological: Pembrolizumab 200 mg; Biological: Pembrolizumab 10 mg/kg; Drug: Carboplatin AUC 5 mg/mL/min

Study type: Interventional

Funder types: Industry

Identifiers

NCT01840579

MK-3475-011 (Other Identifier)

132249 (Registry Identifier)

3475-011

KEYNOTE-011 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 57 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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57 participants in 10 patient groups

Pembrolizumab 2 mg/kg

Experimental group

Description:

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).

Treatment:

Biological: Pembrolizumab 2 mg/kg

Pembrolizumab 10 mg/kg

Experimental group

Description:

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).

Treatment:

Biological: Pembrolizumab 10 mg/kg

Pembrolizumab+Cisplatin/Pemetrexed

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed 500 mg/m^2

Biological: Pembrolizumab 200 mg

Drug: Cisplatin 75 mg/m^2

Pembrolizumab+Carboplatin/Pemetrexed

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed 500 mg/m^2

Drug: Carboplatin AUC 5 mg/mL/min

Biological: Pembrolizumab 200 mg

Pembrolizumab+Carboplatin/Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin AUC 6 mg/mL/min

Biological: Pembrolizumab 200 mg

Drug: Paclitaxel 200 mg/m^2

Pembrolizumab+Carboplatin/Nab-paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin AUC 6 mg/mL/min

Drug: Nab-paclitaxel 100 mg/m^2

Biological: Pembrolizumab 200 mg

Pembrolizumab+Ipilimumab

Experimental group

Description:

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).

Treatment:

Biological: Pembrolizumab 200 mg

Biological: Ipilimumab 1 mg/kg

Pembrolizumab+Cisplatin/Etoposide

Experimental group

Description:

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.

Treatment:

Drug: Etoposide 100 mg/m^2

Biological: Pembrolizumab 200 mg

Drug: Cisplatin 75 mg/m^2

Pembrolizumab+Carboplatin/Etoposide

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin AUC 5 mg/mL/min

Drug: Etoposide 100 mg/m^2

Biological: Pembrolizumab 200 mg

Pembrolizumab+Cisplatin/Etoposide+G-CSF

Experimental group

Description:

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.

Treatment:

Biological: Pembrolizumab 200 mg

Drug: Cisplatin 75 mg/m^2

Drug: G-CSF (pegfilgrastim) 3.6 mg