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)

Non-small Cell Lung Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02039674
• Other study ID #: 3475-021
• Secondary ID: MK-3475-021KEYNO
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 21, 2014
• Est. completion date: October 18, 2021

Study information

• Verified date: October 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 267
• Est. completion date: October 18, 2021
• Est. primary completion date: November 7, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Carcinoma

Intervention

Biological:
• Pembrolizumab
IV on Day 1 of each 3-week cycle prior to chemo/immunotherapy

Drug:
• Paclitaxel
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations
• Carboplatin
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations

Biological:
• Bevacizumab
IV on Day 1 of each 3-week cycle

Drug:
• Pemetrexed
IV on Day 1 of each 3-week cycle

Biological:
• Ipilimumab
IV on Day 1 of each 3-week cycle for a maximum of 4 administrations

Drug:
• Erlotinib
Orally tablet once daily
• Gefitinib
Oral tablet once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

References & Publications (2)

Borghaei H, Langer CJ, Gadgeel S, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, Panwalkar A, Yang JC, Gubens M, Sequist LV, Awad MM, Fiore J, Saraf S, Keller SM, Gandhi L. 24-Month Overall Survival from KEY — View Citation

Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, Panwalkar A, Yang JC, Gubens M, Sequist LV, Awad MM, Fiore J, Ge Y, Raftopoulos H, Gandhi L; KEYNOTE-021 investigators. Carbo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 2 Cohorts G+ and G-: Objective Response Rate (ORR)	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).	Up to approximately 2 years
Primary	Part 2 Cohorts D4 and H: Objective Response Rate (ORR)	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.	Up to approximately 2 years
Primary	All Cohorts: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)	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.	Cycle 1 (Up to 21 days)
Secondary	Part 2 Cohorts G+ and G-: Progression-Free Survival (PFS)	PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was assessed by BICR.	Up to approximately 2 years
Secondary	Part 2 Cohorts G+ and G-: Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	Up to approximately 2 years
Secondary	Part 2 Cohorts G+ and G-: Duration of Response (DOR)	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.	Up to approximately 2 years

External Links

•   Merck Oncology Clinical Trials Information