Imfinzi significantly improved event-free survival in AEGEAN Phase III trial for patients with resectable non-small cell lung cancer

AstraZeneca announced that their pivotal P3 AEGEAN trial investigating neoadj. durva + chemo followed by adj. durva monotherapy in resectable early-stage (IIA-IIIB) NSCLC has met one of its dual primary endpoints of EFS compared to neoadj. placebo + chemo at interim analysis. Statistically significant and meaningful improvements in pathologic complete response (pCR) and major pathologic response (mPR) were previously announced in June 2022.

TThe 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 durva + chemo followed by adj. durva monotherapy met its EFS primary endpoint versus neoadj. chemo alone followed by surgery for patients with resectable early-stage (IIA-IIIB) NSCLC
  • data from the final pCR and mPR analyses were consistent with previously announced positive interim results
  • The trial will continue as planned to evaluate key secondary endpoints, including DFS and OS
• approvals are expected for the US in 2Q2024 and EU in 3Q2024
• If approved, perioperative durva would enter a competitive landscape which already includes several approved IOs in neoadj. or adj. NSCLC and would potentially compete with recently filed perioperative pembro (if approved based on P3 KEYNOTE-671 trial)
  • If both perioperative durva and pembro are approved, it is unclear how physicians will differentiate between available IO treatments. P3 KEYNOTE-671 and P3 AEGEAN are very similar trials with identical staging (specified “stage II, IIIA and IIIB” vs “stage IIA-IIIB,” respectively)
  • EFS and safety data from both trials will be closely considered to inform treatment choice between perioperative durva and perioperative pembro
  • Lastly, as perioperative treatments, durva (and pembro) will likely have to at least meet the benchmark set by neoadj. nivolumab based P3 Checkmate-816 (mEFS: 31.6mo; HR=0.63 vs chemo) to support the rationale of using IO both pre- and post-surgery in resectable NSCLC patients
• it remains unclear how to sequence IOs across the early-stage and metastatic settings for patients that progress after perioperative treatment, pointing to a need for data supporting IO re-challenge.

Background:

• P3 AEGEAN (NCT03800134): neoadj. durva + chemo in stage II and III resectable NSCLC including EGFR/ALK+ mutations
  • Key Trial Details:
    • N = 825
    • 1EP: EFS, pCR
    • 2EP: DFS, mPR, OS in ITT; EFS, pCR, DFS, mPR, OS in PD-L1 >1% QoL
  • 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 KEYNOTE-671 (NCT03425643): neoadj. pembro + chemo followed by adj. pembro vs neoadj. chemo + placebo in resectable stage II, IIIA, IIIB NSCLC
      • Topline read-out: EFS Mar 1, 2023
    • P3 CheckMate 77T (NCT04025879): perioperative nivo + chemo in stage IIB-IIIB resectable NSCLC
      • Topline read-out: EFS 4Q2023
    • Durva is approved in the curative-intent setting of unresectable Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy in the US, Japan, China, across the EU and many other countries, and is the global standard of care in this setting based on the PACIFIC Phase III trial. Durva is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial.
      • Ongoing registrational durvalumab studies include resectable NSCLC (MERMAID-1), unresectable NSCLC (PACIFIC-2, 4, 5, 8 and 9), and in limited-stage small cell lung cancer (SCLC) (ADRIATIC)