Clinical trial NCT02039674: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Carcinoma
Keywords: PD-1
PD1
Programmed Cell Death-1
Programmed Cell Death 1
Chemotherapy
Pemetrexed
Paclitaxel
Bevacizumab
Erlotinib
Gefitinib
Ipilimumab
Carboplatin
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-01-17
Enrollment: 267
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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
* 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

Primary outcomes:
measure: Part 2 Cohorts G+ and G-: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
measure: Part 2 Cohorts D4 and H: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
measure: All Cohorts: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
timeFrame: Cycle 1 (Up to 21 days)
Secondary outcomes:
measure: Part 2 Cohorts G+ and G-: Progression-Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Part 2 Cohorts G+ and G-: Overall Survival (OS)
timeFrame: Up to approximately 2 years
measure: Part 2 Cohorts G+ and G-: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016 Nov;17(11):1497-1508. doi: 10.1016/S1470-2045(16)30498-3. Epub 2016 Oct 10.
citation: 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 KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. J Thorac Oncol. 2019 Jan;14(1):124-129. doi: 10.1016/j.jtho.2018.08.004. Epub 2018 Aug 21.
citation: Yang JC, Gadgeel SM, Sequist LV, Wu CL, Papadimitrakopoulou VA, Su WC, Fiore J, Saraf S, Raftopoulos H, Patnaik A. Pembrolizumab in Combination With Erlotinib or Gefitinib as First-Line Therapy for Advanced NSCLC With Sensitizing EGFR Mutation. J Thorac Oncol. 2019 Mar;14(3):553-559. doi: 10.1016/j.jtho.2018.11.028. Epub 2018 Dec 4.
citation: Gadgeel SM, Stevenson JP, Langer CJ, Gandhi L, Borghaei H, Patnaik A, Villaruz LC, Gubens M, Hauke R, Yang JC, Sequist LV, Bachman R, Saraf S, Raftopoulos H, Papadimitrakopoulou V. Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. Lung Cancer. 2018 Nov;125:273-281. doi: 10.1016/j.lungcan.2018.08.019. Epub 2018 Aug 25.