Pepinemab–avelumab combo shows promising antitumour activity in NSCLC

Combination therapy with pepinemab plus avelumab is well tolerated and appears to have therapeutic potential in advanced non–small cell lung cancer (NSCLC), including immunotherapy-resistant and PD-L1-negative/-low tumours, according to the results of a phase Ib/II trial.

The single-arm trial involved 62 advanced NSCLC patients; 12 immunotherapy-naïve (ION) patients were enrolled in phase Ib, with pepinemab given at 5 mg/kg in three patients, 10 mg/kg in six, and 20 mg/kg in three. The remaining 50 patients were enrolled in phase II, of whom 18 were ION and 32 had disease that progressed following anti-PD-1/L1 monotherapy (IOF).

Among patients with IOF, seven experienced primary resistance and 18 had acquired resistance to immune checkpoint inhibitors. Only one patient in the entire cohort had a tumour with high PD-L1 expression.

The combination was well tolerated, and no major safety signals emerged. Grade 1 or 2 fatigue and infusion-related reactions were the most common adverse events. Pepinemab at 10 mg/kg plus avelumab 10 mg/kg, administered every 2 weeks, was selected as the recommended phase 2 dose.

In the ION group, five patients achieved partial response (PR), 12 had a stable disease, and four experienced progression. The corresponding disease control rate (DCR) was 81 percent. Four patients achieved durable response (≥1 year). The objective response rate was 24 percent (5/21), and the median progression-free survival was 11.6 weeks.

In the IOF group, treatment yielded a DCR of 59 percent. Two patients exhibited PR, and seven had durable clinical benefit of ≥23 weeks.

Biomarker analysis of biopsies showed high CD8 T-cell density to be correlated with RECIST response criteria.