492P - Penpulimab-based combination neoadjuvant/adjuvant therapy for patients with resectable locally advanced non-small cell lung cancer: Preliminary results from a phase II study (ALTER-L043)

Background

The Perioperative combinations including immune checkpoint inhibitors (ICIs) have shown encouraging results in patients with resectable locally advanced NSCLC, but the better treatment option needs to be explored further. Anti-angiogenesis therapy has been reported to adjust tumor microenvironment and synergistic effects of immunotherapy. We made an advanced design to investigate the efficacy and safety of Penpulimab-based combination neoadjuvant/adjuvant therapy for this population.

Methods

In this multicenter phase II study, eligible patients (pts) without driver gene mutations, resectable clinical stage IIB-IIIB (N2) NSCLC, were randomized 1:1:1 to receive one of the three regimens in 21-day cycle: Penpulimab (200mg, iv, day 1) + chemotherapy + Anlotinib (12mg, po, day 1-14) (Arm A) or Penpulimab (200mg, iv, day 1) + chemotherapy (Arm B) or Penpulimab (200mg, iv, day 1) + Anlotinib (12mg, po, day 1-14) (Arm C) for 3-4 cycles before surgery, followed by adjuvant therapy of Penpulimab + Anlotinib (Arm A, C) or Penpulimab monotherapy (Arm B) for a year at most. Primary endpoint was major pathological response (MPR) rate, secondary endpoints were objective response rate (ORR), pathologic complete response (pCR), event-free survival (EFS), 1 year EFS rate, overall survival (OS) and safety.

Results

From December, 2021 to August, 2023, 49 pts were randomized to Arm A (n=16) or Arm B (n=16) or Arm C (n=17). At data cutoff (Aug 3, 2023), median follow-up was 5.3 months. Definitive surgery rates in Arm A/B/C were 87.5% vs 87.5% vs 76.5% respectively. The MPR rates were 70.0% vs 37.5% vs 80% in the three arms, and 50.0% vs 37.5% vs 60% pts showed pCR respectively. ORR of neoadjuvant therapy was 50.0% vs 37.5% vs 47.06% in the three arms. The incidence of grade ≥ 3 adverse events (AEs) were 31.25% vs 31.25% vs 23.53% respectively. There is no fatal AE related to Penpulimab or Anlotinib.

Conclusions

The results demonstrated that these new perioperative combinations of ICI and Anti-angiogenesis agent (Penpulimab and Anlotinib) with or without chemotherapy showed promising efficacy and with manageable safety profiles.

Clinical trial identification

NCT04846634.

Editorial acknowledgement

Legal entity responsible for the study

Tianjin Medical University Cancer Institute & Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.