A Study of Pembrolizumab (MK-3475) in Combination With Chemotherapy or Immunotherapy in Participants With Non-small Cell Lung Cancer (MK-3475-021/KEYNOTE-021)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Non-small Cell Lung Carcinoma

Treatments: Biological: Bevacizumab; Drug: Carboplatin; Drug: Pemetrexed; Drug: Gefitinib; Biological: Pembrolizumab; Drug: Paclitaxel; Biological: Ipilimumab; Drug: Erlotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02039674

MK-3475-021 (Other Identifier)

KEYNOTE-021 (Other Identifier)

3475-021

Details and patient eligibility

About

The purpose of this study is to determine the safety, tolerability, and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy or immunotherapy in participants with unresectable or metastatic non-small cell lung cancer (NSCLC).

Enrollment: 267 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Stage IIIb/IV NSCLC
• Disease progression >1 year after completing adjuvant therapy for Stage I-IIIA disease and no systemic therapy for the recurrent disease
• Resolution of any toxic effects (excepting alopecia) of the most recent therapy
• At least one radiographically measurable lesion
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status scale
• 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 or tyrosine kinase inhibitors

Exclusion criteria

• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of administration of pembrolizumab
• Expected to require any other form of antineoplastic therapy while on study
• Is on chronic systemic steroid therapy or on any other form of immunosuppressive medication
• Has received a live-virus vaccination within 30 days of planned treatment start
• Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)
• History of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the participant has undergone potentially curative therapy with no evidence of that disease for 5 years
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
• Active autoimmune disease that has required systemic treatment in the past 2 years (replacement therapies for hormone deficiencies are allowed)
• Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immuno-regulatory receptors or mechanisms
• Systemic cytotoxic chemotherapy, antineoplastic biologic therapy, or major surgery within 3 weeks of the first dose of study medication
• Radiation therapy to lung >30 Gy within 6 months of first dose of study medication
• Prior tyrosine kinase inhibitor therapy or palliative radiation within 7 days of first dose of study medication
• Active infection requiring therapy
• History of Human Immunodeficiency Virus (HIV)
• Active Hepatitis B or C
• Symptomatic ascites or pleural effusion
• Interstitial lung disease or pneumonitis requiring oral or IV glucocorticoids
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
• Psychiatric disorders and substance (drug/alcohol) abuse

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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267 participants in 14 patient groups

Part 1 Cohort A2 (Pembro2mg/kg+Paclitaxel [Pa]+Carboplatin [C])

Experimental group

Description:

Cohort A participants receive pembrolizumab (2 mg/kg) via intravenous (IV) infusion on Day 1 of each 3-week cycle PLUS paclitaxel (200 mg/m\^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (Aare Under the Curve \[AUC\] 6 \[6 mg/mL/min\]) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Drug: Paclitaxel

Biological: Pembrolizumab

Drug: Carboplatin

Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B])

Experimental group

Description:

Cohort B2 participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (200 mg/m\^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 6 \[6 mg/mL/min\]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (15 mg/kg) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Drug: Paclitaxel

Biological: Pembrolizumab

Drug: Carboplatin

Biological: Bevacizumab

Part 1 Cohort C2 (Pembro 2mg/kg+Pemetrexed [Pe]+C)

Experimental group

Description:

Cohort C2 participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (500 mg/m\^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 5 \[5 mg/mL/min\]) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Biological: Pembrolizumab

Drug: Pemetrexed

Drug: Carboplatin

Part 1 Cohort D1 (Pembro 10mg/kg+Ipilimumab [I])

Experimental group

Description:

Cohort D1 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (1 mg/kg) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Biological: Ipilimumab

Biological: Pembrolizumab

Part 1 Cohort E (Pembro 2mg/kg+Erlotinib)

Experimental group

Description:

Cohort E participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS erlotinib (150 mg) via oral tablet once a day on every day of each 3-week cycle.

Treatment:

Drug: Erlotinib

Biological: Pembrolizumab

Part 1 Cohort F (Pembro 2mg/kg+Gefitinib)

Experimental group

Description:

Cohort F participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS gefitinib (250 mg) via oral tablet once a day on every day of each 3-week cycle.

Treatment:

Biological: Pembrolizumab

Drug: Gefitinib

Part 2 Cohort G+ (Pembro 200mg+C+Pe)

Experimental group

Description:

Cohort G+ participants receive pembrolizumab (200 mg) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 5 \[5 mg/mL/min\]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (500 mg/m\^2) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Biological: Pembrolizumab

Drug: Pemetrexed

Drug: Carboplatin

Part 2 Cohort H (Pembro+I)

Experimental group

Description:

Cohort H participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (1 mg/kg) via IV infusion on Day 1 of each 3-week cycle (at the recommended Phase II dose determined in Cohort D).

Treatment:

Biological: Ipilimumab

Biological: Pembrolizumab

Part 1 Cohort A10 (Pembro+Paclitaxel [Pa]+Carboplatin [C])

Experimental group

Description:

Cohort A10 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (200 mg/m\^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 6 \[mg/mL/min\]) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Drug: Paclitaxel

Biological: Pembrolizumab

Drug: Carboplatin

Part 1 Cohort B10 (Pembro+Pa+C+Bevacizumab [B])

Experimental group

Description:

Cohort B10 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS paclitaxel (200 mg/m\^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 6 \[6 mg/mL/min\]) via IV infusion on Day 1 of each 3-week cycle PLUS bevacizumab (15 mg/kg) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Drug: Paclitaxel

Biological: Pembrolizumab

Drug: Carboplatin

Biological: Bevacizumab

Part 1 Cohort C10 (Pembro 10mg/kg+Pemetrexed [Pe]+C)

Experimental group

Description:

Cohort C10 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (500 mg/m\^2) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 5 \[5 mg/mL/min\]) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Biological: Pembrolizumab

Drug: Pemetrexed

Drug: Carboplatin

Part 2 Cohort G- (Placebo+C+Pe)

Experimental group

Description:

Cohort G- participants receive placebo (normal saline solution) via IV infusion on Day 1 of each 3-week cycle PLUS carboplatin (AUC 5 \[5 mg/mL/min\]) via IV infusion on Day 1 of each 3-week cycle PLUS pemetrexed (500 mg/m\^2) via IV infusion on Day 1 of each 3-week cycle PLUS.

Treatment:

Drug: Pemetrexed

Drug: Carboplatin

Part 1 Cohort D2 (Pembro 10mg/kg+Ipilimumab [I])

Experimental group

Description:

Cohort D2 participants receive pembrolizumab (10 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (3 mg/kg) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Biological: Ipilimumab

Biological: Pembrolizumab

Part 1 Cohort D4 (Pembro 2mg/kg+Ipilimumab [I])

Experimental group

Description:

Cohort D1 participants receive pembrolizumab (2 mg/kg) via IV infusion on Day 1 of each 3-week cycle PLUS ipilimumab (1 mg/kg) via IV infusion on Day 1 of each 3-week cycle.

Treatment:

Biological: Ipilimumab

Biological: Pembrolizumab