WCLC 2024: Adding JAK1 Inhibitor to Pembrolizumab in Metastatic PD-L1–Positive NSCLC

By: Julia Cipriano, MS
Posted: Thursday, September 26, 2024

According to Melina E. Marmarelis, MD, MSCE, of the University of Pennsylvania, Philadelphia, and colleagues, patients with metastatic PD-L1–positive non–small cell lung cancer (NSCLC) who were treated in the first-line setting with the PD-1 inhibitor pembrolizumab plus the JAK inhibitor itacitinib achieved a 12-week overall response rate of 62% and improved median progression-free and overall survival vs historical controls. These findings from a long-term follow-up analysis of a phase II trial were presented during the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC; Abstract OA06.04).

“Interferon signaling modulation through JAK1 inhibition may help prevent resistance to anti–PD-1 therapy and should be studied further in a randomized trial,” the investigators commented.

A total of 23 treatment-naive patients (median age, 62 years) with a PD-L1 expression level of at least 50% and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were administered 200 mg of intravenous pembrolizumab every 21 days. They initiated treatment with 200 mg of oral itacitinib daily on the first day of the third cycle of pembrolizumab, continuing it for 6 weeks.

Among the 20 patients who completed 12 weeks of treatment, the overall response rate was 62%; this included 13 with a partial response, 6 with stable disease, and 2 with progressive disease. The best overall response rate was 66.7%; 2 patients had a complete response, 12 had a partial response, 6 had stable disease, and 1 had progressive disease. The median progression-free and overall survival were 12.7 (vs 10.3 months in KEYNOTE-024) and 53.4 (vs 30.0 months) months, respectively. These durations did not appear to differ between the patients with PD-L1 expression of up to 89% (n = 14) and those with levels of at least 90% (n = 9).

Disclosure: For full disclosure information, visit wclc2024.iaslc.org.

2024 World Conference on Lung Cancer