145P - Penpulimab-based combination neoadjuvant/adjuvant therapy for patients with resectable locally advanced non-small cell lung cancer: An update of the phase II, prospective study (ALTER-L043)

Background

Perioperative immunotherapy has become a new standard of care in resectable locally advanced NSCLC. However, the optimal neoadjuvant and adjuvant treatment are unknown. Angiogenesis inhibitors have been reported to adjust tumor microenvironment and synergistic effects of immunotherapy. Here, we present updated efficacy and safety data of Penpulimab-based combination neoadjuvant/adjuvant therapy for this population in ALTER-L043.

Methods

Patients (pts) with resectable stage IIB-IIIB (N2) NSCLC, without driver gene mutations, 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

A total of 90 pts were randomized to Arm A (n=30) or Arm B (n=30) or Arm C (n=30). At data cutoff on Sep 30, 2024, median follow-up was 12.8 months. Definitive surgery rates in Arm A/B/C were 62.5% vs 89.7% vs 70.0% respectively. The MPR rates of intention to treat (ITT) population were 76.0% vs 57.7% vs 52.4% in the three arms, and 52.0% vs 50.0% vs 38.1% pts showed pCR respectively. ORR of neoadjuvant therapy was 77.8% vs 58.6% vs 63.3% in the three arms. The incidence of grade ≥ 3 adverse events (AEs) were 46.7% vs 36.7% vs 13.3% 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.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.