59MO Final analysis of AK105-302: A randomized, double-blind, placebo-controlled, phase III trial of penpulimab plus carboplatin and paclitaxel as first-line treatment for advanced squamous NSCLC

Penpulimab is a novel humanized IgG1 mAb that blocks PD-1 binding to PD-L1, engineered to eliminate FcγR binding and ADCC/ADCP completely. AK105-302 is a 1:1 randomized, double-blind, placebo-controlled, multicenter, phase III trial to compare penpulimab or placebo plus carboplatin and paclitaxel as first-line treatment for locally advanced or metastatic squamous NSCLC. The stratification factors included PD-L1 and gender. Eligible pts were randomized 1:1 to receive penpulimab 200 mg or placebo plus chemotherapy every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy until disease progression or 24 months, subjects in placebo group may choose to cross over to open-label penpulimab monotherapy for up to 24 months. The primary endpoints were PFS in the ITT population and in the PD-L1-positive population (TPS of PD-L1≥1%), assessed by an IRRC. The secondary endpoints were OS, ORR, DoR, DCR and TTR. 175 pts were assigned to penpulimab plus chemotherapy (P+C) and 175 to placebo plus chemotherapy (C). At data cutoff (Jun 1, 2022), the median follow-up was 23.56m. The mPFS by IRRC was significantly longer with P+C than with C (7.6m vs. 4.2m; HR 0.44, 95%CI: 0.34-0.56; p < 0.0001), 12m-PFS rate (37.1% vs. 9.2%) and 24m-PFS rate (23.8% vs. 5.9%) were significantly higher in P+C than C. In the PD-L1-positive population, the mPFS by IRRC was also significantly longer with P+C than with C (8.1m vs. 4.2m; HR 0.37, 95%CI: 0.27-0.51; p < 0.0001). The mOS of P+C was not reached, but the benefit trend was obvious (NR vs. 19.8m; HR 0.55, 95%CI: 0.40-0.75; p = 0.0002), 24m-OS rate (61.1% vs. 41.6%) were significantly higher in P+C than C. ORR by IRRC was 71.4% in P+C and 44.0% in C. Treatment with P+C was associated with more durable response (mDoR by IRRC: 8.25m vs 2.96m) than C. Grade ≥3 TRAEs occurred in 63.6% (P+C) vs. 62.9% (C). Serious TRAEs occurred in 28.3% (P+C) vs. 26.9% (C). TRAEs led to treatment discontinuation were 5.2% in P+C and 3.4% in C. These positive data will support penpulimab plus chemotherapy may be a promising and safe first-line treatment for locally advanced or metastatic squamous NSCLC.