Merck announced Phase 3 KEYNOTE-671 Trial met Primary Endpoint of Event-Free Survival (EFS) in patients with resectable stage II, IIIA or IIIB Non-Small Cell Lung Cancer (NSCLC)

On March 1, 2023, Merck announced that their pivotal P3 KEYNOTE-671 trial investigating neoadjuvant pembro + chemo followed by adjuvant pembro in resectable stage II, IIIA or IIIB NSCLC has met one of its dual primary endpoints of EFS at interim analysis and has already been filed with the FDA.

The evolving treatment paradigm in resectable NSCLC will need to be taken into consideration for any future trial designs for Gilead therapies in this segment.

Highlights and Implications:

• Neoadjuvant pembro + chemo followed by surgery and adjuvant pembro showed statistically significant and clinically meaningful improvement in EFS compared to neoadj. placebo + chemo followed by adjuvant placebo
  • The regimen also showed statistically significant improvements in the secondary endpoints of pathological complete response (pCR) and major pathological response (mPR)
  • The trial will continue to evaluate the other dual primary endpoint of OS (no further timeline details were provided)
• FDA has accepted Merck’s new sBLA based on these data and has set a PDUFA date of October 16, 2023 (application will be evaluated under regular review)
  • assumptions on US approval in 4Q2023, and EU approval is 2Q2024
• If approved, pembro would be the first approved perioperative treatment in NSCLC, entering a landscape that has seen increased competitiveness due to several recent approvals for IO in adjuvant or neoadjuvant use
  • It will be important to see how results from KEYNOTE-671 compare to BMS’s CheckMate 816 study of neoadjuvant nivo + chemo (no adjuvant component), as physicians and payers will likely want to see an additional EFS benefit to justify the use of adjuvant pembrolizumab

Additional Background Information

• P3 KEYNOTE-671 (NCT03425643): neoadj. pembro + chemo followed by adj. pembro vs neoadj. chemo + placebo in resectable stage II, IIIA, IIIB NSCLC
  • N = 786
  • 1EP: Event Free Survival (EFS), Overall Survival (OS)
  • 2EP: Major Pathological Response (mPR) rate, Pathological Complete Response (Pcr) rate, Global Health Status/Quality of Life (GHS/QoL), Adverse Events (AEs), Perioperative Complications, Treatment Discontinuations Due to AEs
• Recently approved IO in resectable NSCLC include:
  • nivolumab + chemo (approved in Mar. 2022; based on P3 CheckMate-816)
  • adjuvant atezo following chemo (approved in Oct. 2021; based on P3 IMpower010)
  • adjuvant pembro following chemo (approved in Jan. 2023; based on P3 KEYNOTE-091)
• Other ongoing P3 perioperative IO trials (data readouts and/or regulatory filings expected later in 2023 and in 2024):
  • P3 IMpower030 (NCT03456063): perioperative atezo + chemo vs placebo + chemo in stage II-IIIB, resectable NSCLC
    • Topline read-out: EFS 1Q2024
  • P3 AEGEAN (NCT03800134): perioperative durvalumab + chemo in stage II and III resectable NSCLC
    • Topline EFS read-out: EFS 2Q2023
    • pCR coprimary endpoint announced as positive in June 2022
  • P3 CheckMate 77T (NCT04025879): perioperative nivo + chemo in stage IIB-IIIB resectable NSCLC
    • Topline read-out: EFS 4Q2023