KEY TAKEAWAYS
- The ALTER-L043 Phase 2 trial aimed to investigate the efficacy and safety of penpulimab-based combination neoadjuvant/adjuvant therapy in NSCLC pts.
- The primary endpoint was to determine the MPR rate. The secondary endpoints were ORR, pCR, and EFS.
- Researchers noticed promising efficacy and manageable safety observed in combo penpulimab and anlotinib for resectable locally advanced NSCLC.
The perioperative use of immune checkpoint inhibitors (ICIs) has shown promise in treating resectable locally advanced non-small cell lung cancer (NSCLC). However, the optimal treatment remains to be determined. Anti-angiogenesis therapy has demonstrated the ability to modulate the tumor microenvironment (TME) and enhance the synergistic effects of immunotherapy.
In response to these considerations, Changli Wang and his team aimed to investigate the efficacy and safety of penpulimab-based combination neoadjuvant/adjuvant therapy for patients (pts) with resectable locally advanced NSCLC.
The study performed an inclusive analysis in a multicenter phase II setting, enrolling eligible patients diagnosed with resectable clinical stage IIB-IIIB (N2) NSCLC without driver gene mutations. Pts were randomized in a 1:1:1 ratio to receive one of three regimens in a 21-day cycle: Arm A – penpulimab (200mg, iv, day 1) + chemotherapy + Anlotinib (12mg, po, day 1-14), Arm B – penpulimab (200mg, iv, day 1) + chemotherapy, or Arm C – penpulimab (200mg, iv, day 1) + Anlotinib (12mg, po, day 1-14). The treatment duration comprised 3-4 cycles before surgery, followed by adjuvant therapy with penpulimab + Anlotinib (Arms A and C) or penpulimab monotherapy (Arm B) for a maximum of one year.
The primary endpoint was the major pathological response (MPR) rate, with secondary endpoints including objective response rate (ORR), pathologic complete response (pCR), event-free survival (EFS), 1-year EFS rate, overall survival (OS), and safety.
About 49 pts were randomized from December 2021 to August 2023, with 16 in Arm A, 16 in Arm B, and 17 in Arm C. At the data cutoff on August 3, 2023, the median follow-up period was 5.3 months. The definitive surgery rates for Arms A, B, and C were 87.5%, 87.5%, and 76.5%, respectively.
Regarding MPR rates, Arm A showed 70.0%, Arm B showed 37.5%, and Arm C demonstrated 80%. pCR rates were 50.0%, 37.5%, and 60% in Arms A, B, and C, respectively. The ORR for neoadjuvant therapy was 50.0% in Arm A, 37.5% in Arm B, and 47.06% in Arm C.
The incidence of grade ≥ 3 adverse events (AEs) was 31.25% in Arm A, 31.25% in Arm B, and 23.53% in Arm C. Importantly, there were no fatal AEs related to Penpulimab or Anlotinib observed during the study period.
The study concluded that the new perioperative combinations involving ICIs and anti-angiogenesis agents (penpulimab and anlotinib), whether administered with or without chemotherapy, exhibited promising efficacy and demonstrated manageable safety profiles.
The study is sponsored by Tianjin Medical University Cancer Institute and Hospital
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/78
Clinical Trial: https://clinicaltrials.gov/study/NCT04846634
Wang C, Wang M, Long H, et al. (2023). “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).” Presented at ESMO ASIA 2023 (Abstract 492P).
