Biomarkers of Response to Pembrolizumab Combined With Chemotherapy in Non-Small Cell Lung Cancer (KEYNOTE-782, MK-3475-782) (KEYNOTE-782)
|ClinicalTrials.gov Identifier: NCT03664024|
Recruitment Status : Active, not recruiting
First Posted : September 10, 2018
Last Update Posted : February 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Lung Cancer||Drug: Pembrolizumab Drug: Pemetrexed Drug: Carboplatin Drug: Cisplatin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial to Investigate Genetic Markers of Response to Pembrolizumab (MK-3475, SCH 900475) Combined With Chemotherapy as a First-line Treatment for Non-Small Cell Lung Cancer (KEYNOTE-782)|
|Actual Study Start Date :||October 30, 2018|
|Estimated Primary Completion Date :||July 14, 2021|
|Estimated Study Completion Date :||July 14, 2021|
Experimental: Pembrolizumab Standard of Care
Participants will receive standard of care pembrolizumab combined with platinum-doublet chemotherapy for 4 cycles, then pembrolizumab plus pemetrexed maintenance for up to 31 additional cycles. The platinum doublet would be pemetrexed plus the investigator's choice of either cisplatin or carboplatin.
Pembrolizumab, 200 mg, Day 1 of each 21-day cycle (Q3W), intravenous infusion (IV), standard of care in most countries
Pemetrexed, 500 mg/m^2 infusion, standard of care, Q3W, IV
Carboplatin AUC 5 mg/mL/min, IV infusion, Day 1 of each 21-day cycle for 4 cycles (Cycles 1 - 4). Investigator's choice of either cisplatin or carboplatin.
Cisplatin, 75 mg/m^2, IV infusion, Day 1 of each 21-day cycle for 4 cycles (Cycles 1 - 4). Investigator's choice of either cisplatin or carboplatin.
- Objective Response (OR) [ Time Frame: Up to approximately 25 months ]Objective response rate is the proportion of participants who have a confirmed complete response (CR) or partial response (PR). Objective response rate is assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Tumor Mutation Burden (TMB) [ Time Frame: Baseline ]Circulating cell-free DNA (cfDNA) allows the exploration of the mechanisms of progression on and resistance to pembrolizumab and chemotherapy, and assesses the role of the metagenomics (microbiome) and metabolomics in response to pembrolizumab + chemotherapy in NSCLC. The tumor mutation burden in circulating cfDNA will be estimated in blood.
- Progression Free Survival (PFS) [ Time Frame: Up to approximately 25 months ]PFS is defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- Overall Survival (OS) [ Time Frame: Up to approximately 25 months ]OS is defined as the time from the start of treatment to death due to any cause.
- Adverse Events (AEs) [ Time Frame: Up to 30 days after last dose of study treatment (Up to approximately 26 months) ]Percentage of participants who experienced one or more AEs.
- Discontinuations from Study Drug Due to an Adverse Event [ Time Frame: Up to approximately 25 months ]Percentage of participants discontinuing study treatment(s) due to an AE.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03664024
|United States, Colorado|
|University Of Colorado ( Site 0908)|
|Aurora, Colorado, United States, 80045|
|United States, Maryland|
|Harry & Jeanette Weinberg Cancer Institute ( Site 0901)|
|Baltimore, Maryland, United States, 21237|
|United States, Michigan|
|Henry Ford Health System ( Site 0903)|
|Detroit, Michigan, United States, 48202|
|Kingston General Hospital ( Site 0800)|
|Kingston, Ontario, Canada, K7L 2V7|
|CISSS de la Monteregie-Centre ( Site 0801)|
|Greenfield Park, Quebec, Canada, J4V 2H1|
|Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 0400)|
|Budapest, Hungary, 1121|
|Petz Aladar Megyei Oktato Korhaz ( Site 0402)|
|Gyor, Hungary, 9024|
|Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0401)|
|Szolnok, Hungary, 5000|
|Meir Medical Center ( Site 0501)|
|Kfar-Saba, Israel, 4428164|
|Chaim Sheba Medical Center ( Site 0500)|
|Ramat Gan, Israel, 5262000|
|Hospital Universitario Insular de Gran Canaria ( Site 0700)|
|Las Palmas de Gran Canaria, Gran Canaria, Spain, 35001|
|Hospital Puerta de Hierro ( Site 0702)|
|Majadahonda, Madrid, Spain, 28222|
|H.U. Vall de Hebron ( Site 0701)|
|Barcelona, Spain, 08035|
|Hospital General Universitario 12 de Octubre ( Site 0703)|
|Madrid, Spain, 28041|
|Hospital Universitario Central de Asturias ( Site 0704)|
|Oviedo, Spain, 33011|
|Study Director:||Medical Director||Merck Sharp & Dohme Corp.|