Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KEYNOTE-158.

Abstract

8506 Background: The antitumor activity of pembrolizumab, an IgG4 anti-PD-1 monoclonal antibody, was evaluated in patients (pts) with SCLC in KEYNOTE-158 (NCT02628067), a phase 2 basket study of 11 cancer types. Methods: Enrolled pts were aged ≥18 y with advanced SCLC; had measurable disease per RECIST v1.1; ECOG PS ≤1; incurable disease with prior failure of, progression on, or intolerance to standard therapy; and evaluable tumor samples for PD-L1 (PD-L1 IHC 22C3 pharmDx assay [Agilent Technologies]) and other biomarkers. Pembrolizumab 200 mg Q3W was administered for 2 y or until disease progression or intolerable toxicity. The primary endpoint was ORR. DOR, PFS, and OS were secondary endpoints and were estimated by the Kaplan-Meier method. Tumor imaging was performed every 9 wks for the first year, then every 12 wks. Response was assessed per RECIST v1.1 by independent central radiologic review. PD-L1–positive was defined as PD-L1 combined positive score ≥1. Results: Among 107 SCLC pts, median age was 63 y (range, 24–84) and 85 (79%) had 1–2 prior therapies. At the data cutoff date (Aug 23, 2017), 36 pts (34%) were continuing on-study; median follow-up was 10.1 mo (range, 0.5–17.5). Tumors were PD-L1–positive in 42 pts (39%) and PD-L1–negative in 50 (47%); 0 had microsatellite instability-high (MSI-H) tumors and 83 (78%) had microsatellite-stable (MSS) tumors. ORR was 18.7% (20/107; 95% CI, 11.8–27.4) overall, 35.7% (15/42; 95% CI, 21.6–52.0) in pts with PD-L1–positive tumors, and 6.0% (3/50; 95% CI, 1.3–16.5) in pts with PD-L1–negative tumors. Overall, median DOR had not been reached (range, 2.1+ to 13.2+ mo); 12 pts (77%) had DOR ≥9 mo. Median PFS was 2.0 mo (95% CI, 1.9–2.1) in all pts, 2.1 mo (95% CI, 2.0–9.9) in pts with PD-L1–positive tumors, and 1.9 mo (95% CI, 1.6–2.0) in pts with PD-L1–negative tumors. Median OS was 9.1 mo (95% CI, 5.7–14.6) overall, 14.6 mo (5.6–not estimable) in pts with PD-L1–positive tumors, and 7.7 mo (95% CI, 3.9–10.4) in pts with PD-L1–negative tumors. Treatment-related AEs occurred in 63 pts (59%) and led to 4 discontinuations and 1 death (pneumonia). Conclusions: Pembrolizumab has shown promising antitumor activity and durable responses in advanced SCLC, especially in pts with PD-L1–positive tumors. Clinical trial information: NCT02628067.