Clinical Trials/NCT02039674

NCT02039674

Completed

Phase 1

A Phase I/II Study of MK-3475 (SCH900475) in Combination With Chemotherapy or Immunotherapy in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Carcinoma

Merck Sharp & Dohme LLC0 sites267 target enrollmentFebruary 21, 2014

ConditionsNon-small Cell Lung Carcinoma

InterventionsPembrolizumab Paclitaxel Carboplatin Bevacizumab Pemetrexed Ipilimumab Erlotinib Gefitinib

DrugsPaclitaxel Carboplatin Pemetrexed Erlotinib Gefitinib

Overview

Phase: Phase 1
Intervention: Pembrolizumab
Conditions: Non-small Cell Lung Carcinoma
Sponsor: Merck Sharp & Dohme LLC
Enrollment: 267
Primary Endpoint: Part 2 Cohorts G+ and G-: Objective Response Rate (ORR)
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

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).

Registry

clinicaltrials.gov

Start Date

February 21, 2014

End Date

October 18, 2021

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Merck Sharp & Dohme LLC

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

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

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.

Intervention: Pembrolizumab

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

Intervention: Paclitaxel

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

Intervention: Carboplatin

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

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.

Intervention: Pembrolizumab

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

Intervention: Paclitaxel

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

Intervention: Carboplatin

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

Intervention: Bevacizumab

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

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.

Intervention: Pembrolizumab

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

Intervention: Carboplatin

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

Intervention: Pemetrexed

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

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.

Intervention: Pembrolizumab

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

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.

Intervention: Ipilimumab

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

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.

Intervention: Pembrolizumab

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

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.

Intervention: Erlotinib

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

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.

Intervention: Pembrolizumab

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

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.

Intervention: Gefitinib

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

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.

Intervention: Pembrolizumab

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

Intervention: Carboplatin

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

Intervention: Pemetrexed

Part 2 Cohort H (Pembro+I)

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).

Intervention: Pembrolizumab

Part 2 Cohort H (Pembro+I)

Intervention: Ipilimumab

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

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.

Intervention: Pembrolizumab

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

Intervention: Paclitaxel

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

Intervention: Carboplatin

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

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.

Intervention: Pembrolizumab

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

Intervention: Paclitaxel

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

Intervention: Carboplatin

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

Intervention: Bevacizumab

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

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.

Intervention: Pembrolizumab

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

Intervention: Carboplatin

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

Intervention: Pemetrexed

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

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.

Intervention: Carboplatin

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

Intervention: Pemetrexed

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

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.

Intervention: Pembrolizumab

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

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.

Intervention: Ipilimumab

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

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.

Intervention: Pembrolizumab

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

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.

Intervention: Ipilimumab

Outcomes

Primary Outcomes

Part 2 Cohorts G+ and G-: Objective Response Rate (ORR)

Time Frame: Up to approximately 2 years

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).

Part 2 Cohorts D4 and H: Objective Response Rate (ORR)

Time Frame: Up to approximately 2 years

For participants who demonstrated a confirmed response (Complete Response \[CR\]: Disappearance of all target lesions or Partial Response \[PR\]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR.

All Cohorts: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

Time Frame: Cycle 1 (Up to 21 days)

DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade 4 non-hematologic toxicity (not laboratory); Grade 4 hematologic toxicity lasting ≥7 days; Grade 3 non-hematologic toxicity (not laboratory, specifically nausea, vomiting and diarrhea) lasting \>3 days despite optimal supportive care; Any Grade 3 or Grade 4 non-hematologic laboratory value requiring treatment or hospitalization, or persisting for \>1 week; Febrile neutropenia Grade 3 or Grade 4; Qualifying thrombocytopenia \<25,000/mm\^3; Prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Missing \>10% of erlotinib or gefitinib doses as a result of adverse events (AEs) during the DLT window of observation; or Grade 5 toxicity.

Secondary Outcomes

Part 2 Cohorts G+ and G-: Progression-Free Survival (PFS)(Up to approximately 2 years)
Part 2 Cohorts G+ and G-: Overall Survival (OS)(Up to approximately 2 years)
Part 2 Cohorts G+ and G-: Duration of Response (DOR)(Up to approximately 2 years)