A Phase III, Randomized, Double-blind Trial of Platinum Doublet Chemotherapy +/-Pembrolizumab (MK-3475) as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Non-small Cell Lung Cancer (NSCLC) (KEYNOTE-671)
Overview
- Phase
- Phase 3
- Intervention
- Pembrolizumab
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 797
- Locations
- 227
- Primary Endpoint
- Overall Survival (OS)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This trial will evaluate the safety and efficacy of pembrolizumab (MK-3475) in combination with platinum doublet neoadjuvant chemotherapy (NAC) before surgery [neoadjuvant phase], followed by pembrolizumab alone after surgery [adjuvant phase] in participants with resectable stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer (NSCLC). The primary hypotheses of this study are that neoadjuvant pembrolizumab (vs. placebo) in combination with NAC, followed by surgery and adjuvant pembrolizumab (vs. placebo) will improve: 1) event free survival (EFS) by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); and 2) overall survival (OS).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) NSCLC.
- •If male, must agree to use contraception or practice abstinence as well as refrain from donating sperm during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention.
- •If female, may participate if not pregnant or breastfeeding, and at least one of the following conditions apply: 1) not a woman of childbearing potential (WOCBP); or 2) a WOCBP who agrees to follow contraceptive guidance during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
- •Have available formalin-fixed paraffin embedded (FFPE) tumor tissue sample blocks for submission. If blocks are not available, have unstained slides for submission for central programmed death-ligand 1 (PD-L1) testing.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days of randomization.
- •Have adequate organ function.
Exclusion Criteria
- •Has one of the following tumor locations/types:1) NSCLC involving the superior sulcus; 2) Large cell neuro-endocrine cancer (LCNEC); or 3) Sarcomatoid tumor.
- •Has a history of (non-infectious) pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids.
- •Has an active infection requiring systemic therapy.
- •Has had an allogenic tissue/sold organ transplant.
- •Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
- •Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Has a known history of human immunodeficiency virus (HIV) infection.
- •Has a known history of Hepatitis B or Hepatitis C.
- •Has a known history of active tuberculosis.
Arms & Interventions
NAC + Neoadjuvant/Adjuvant Pembrolizumab
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of pembrolizumab \[200 mg, intravenous (IV); given on cycle day 1\] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin \[75 mg/m\^2, IV; given on cycle day 1\] and either Gemcitabine \[1000 mg/m\^2, IV; given on cycle days 1 and 8\] or Pemetrexed \[500 mg/m\^2, IV; given on cycle day 1\]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab \[200 mg, IV; given on cycle day 1\].
Intervention: Pembrolizumab
NAC + Neoadjuvant/Adjuvant Pembrolizumab
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of pembrolizumab \[200 mg, intravenous (IV); given on cycle day 1\] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin \[75 mg/m\^2, IV; given on cycle day 1\] and either Gemcitabine \[1000 mg/m\^2, IV; given on cycle days 1 and 8\] or Pemetrexed \[500 mg/m\^2, IV; given on cycle day 1\]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab \[200 mg, IV; given on cycle day 1\].
Intervention: Cisplatin
NAC + Neoadjuvant/Adjuvant Pembrolizumab
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of pembrolizumab \[200 mg, intravenous (IV); given on cycle day 1\] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin \[75 mg/m\^2, IV; given on cycle day 1\] and either Gemcitabine \[1000 mg/m\^2, IV; given on cycle days 1 and 8\] or Pemetrexed \[500 mg/m\^2, IV; given on cycle day 1\]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab \[200 mg, IV; given on cycle day 1\].
Intervention: Gemcitabine
NAC + Neoadjuvant/Adjuvant Pembrolizumab
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of pembrolizumab \[200 mg, intravenous (IV); given on cycle day 1\] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin \[75 mg/m\^2, IV; given on cycle day 1\] and either Gemcitabine \[1000 mg/m\^2, IV; given on cycle days 1 and 8\] or Pemetrexed \[500 mg/m\^2, IV; given on cycle day 1\]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab \[200 mg, IV; given on cycle day 1\].
Intervention: Pemetrexed
NAC + Neoadjuvant/Adjuvant Placebo
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of placebo \[normal saline, IV; given on cycle day 1\] in combination with platinum doublet NAC, consisting of cisplatin \[75 mg/m\^2, IV; given on cycle day 1\] and either Gemcitabine \[1000 mg/m\^2, IV; given on cycle days 1 and 8\] or Pemetrexed \[500 mg/m\^2, IV; given on cycle day 1\]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo \[normal saline, IV; given on cycle day 1\].
Intervention: Placebo
NAC + Neoadjuvant/Adjuvant Placebo
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of placebo \[normal saline, IV; given on cycle day 1\] in combination with platinum doublet NAC, consisting of cisplatin \[75 mg/m\^2, IV; given on cycle day 1\] and either Gemcitabine \[1000 mg/m\^2, IV; given on cycle days 1 and 8\] or Pemetrexed \[500 mg/m\^2, IV; given on cycle day 1\]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo \[normal saline, IV; given on cycle day 1\].
Intervention: Cisplatin
NAC + Neoadjuvant/Adjuvant Placebo
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of placebo \[normal saline, IV; given on cycle day 1\] in combination with platinum doublet NAC, consisting of cisplatin \[75 mg/m\^2, IV; given on cycle day 1\] and either Gemcitabine \[1000 mg/m\^2, IV; given on cycle days 1 and 8\] or Pemetrexed \[500 mg/m\^2, IV; given on cycle day 1\]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo \[normal saline, IV; given on cycle day 1\].
Intervention: Gemcitabine
NAC + Neoadjuvant/Adjuvant Placebo
Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of placebo \[normal saline, IV; given on cycle day 1\] in combination with platinum doublet NAC, consisting of cisplatin \[75 mg/m\^2, IV; given on cycle day 1\] and either Gemcitabine \[1000 mg/m\^2, IV; given on cycle days 1 and 8\] or Pemetrexed \[500 mg/m\^2, IV; given on cycle day 1\]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo \[normal saline, IV; given on cycle day 1\].
Intervention: Pemetrexed
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to approximately 5 years
OS is defined as the time from randomization until death from any cause. The OS for all participants is presented (through database cut-off date of 10-Jul-2023).
Event Free Survival (EFS)
Time Frame: Up to approximately 5 years
EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. EFS determined either by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The EFS for all participants is presented (through database cut-off date of 10-Jul-2023).
Secondary Outcomes
- Major Pathological Response (mPR) Rate(Up to approximately 8 weeks following completion of neoadjuvant treatment (up to Study Week 20))
- Pathological Complete Response (pCR) Rate(Up to approximately 8 weeks following completion of neoadjuvant treatment (up to Study Week 20))
- Change From Baseline in Neoadjuvant Phase in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) Score(Baseline (cycle 1 in neoadjuvant phase) and neoadjuvant week 11)
- Change From Baseline in Adjuvant Phase in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) Score(Baseline (cycle 1 in neoadjuvant phase) and adjuvant week 10 (up to Study Week 30))
- Number of Participants Who Experience an Adverse Event (AE)(Up to approximately 71 weeks)
- Number of Participants Who Experience Perioperative Complications(Up to approximately 51 weeks following surgery)
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)(Up to approximately 57 weeks)