Multicenter phase 3 trial of first-line penpulimab plus chemotherapy for advanced squamous non-small cell lung cancer

Penpulimab is a novel PD-1 inhibitor. The phase 3 AK105-302 trial, at 74 centers in China, evaluated first-line penpulimab in combination with paclitaxel and carboplatin for locally advanced or metastatic squamous non-small cell lung cancer. Patients were randomized 1:1 to four cycles of intravenous penpulimab 200 mg or placebo plus chemotherapy every three weeks, followed by penpulimab or placebo maintenance therapy. Primary end point was progression-free survival in the ITT population and in the PD-L1 positive subgroup (tumor proportion score 1% or more). The figure shows that with median 24.7 months of follow-up, in the ITT population the median PFS was 7.6 months with penpulimab plus chemotherapy versus 4.2 months with placebo plus chemotherapy (HR 0.43; p<0.0001; panel A), while in the PD-L1 positive subgroup the median PFS was 8.1 months with penpulimab plus chemotherapy versus 4.2 months with placebo plus chemotherapy (HR 0.37; p<0.0001; panel B), and in the ITT population the median overall survival was not reached with penpulimab plus chemotherapy and was 20.2 months with placebo plus chemotherapy (HR 0.55; p=0.0002). Grade 3 or worse treatment-emergent adverse events occurred in 69% of the patients with penpulimab plus chemotherapy versus 68% of the patients with placebo plus chemotherapy. The authors conclude that addition of penpulimab to first-line chemotherapy significantly improved PFS in patients with advanced squamous NSCLC.