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

Background

Penpulimab is a novel humanized IgG1 mAb that blocks PD-1 binding to PD-L1, engineered to eliminate FcγR binding and ADCC/ADCP completely.

Methods

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.

Results

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.

Conclusions

These positive data will support penpulimab plus chemotherapy may be a promising and safe first-line treatment for locally advanced or metastatic squamous NSCLC.

Clinical trial identification

NCT03866993.

Legal entity responsible for the study

Chai Tai Tianqing Pharmceutical Group Co, Ltd. Akeso Tiancheng, Inc.

Funding

Chai Tai Tianqing Pharmceutical Group Co,Ltd. Akeso Tiancheng, Inc.

Disclosure

All authors have declared no conflicts of interest.