- Keytruda was studied as monotherapy
- Overall response rate of 18.7%
- In patients whose tumors expressed PD-L1 overall response rate was 35.7%
Merck (NYSE: MRK), announced on 6/4/18 interim data from a cohort of the Phase 2 KEYNOTE-158 study evaluating Keytruda, Merck’s anti-PD-1 therapy, as monotherapy in patients with previously treated advanced small cell lung cancer (SCLC). Findings showed an overall response rate (ORR) of 18.7 percent in patients in the SCLC cohort (95% CI, 11.8–27.4), the primary endpoint of the study. Additionally, in a pre-specified exploratory analysis, ORR was 35.7 percent in patients whose tumors expressed PD-L1 with a combined positive score (CPS) of ≥1 (95% CI, 21.6–52.0). These results, as well as other findings from the KEYNOTE-158 (Abstract #8506) cohort in SCLC, are being presented for the first time today at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.
“In this study, Keytruda demonstrated promising overall response rates in the overall population of small cell lung cancer patients, and in patients whose tumors express PD-L1,” said Dr. Hyun Cheol Chung, professor, Cancer Metastasis Research Center, and professor, Yonsei Cancer Center, South Korea. “As an oncologist, I am encouraged by these results evaluating Keytruda as a monotherapy in a type of lung cancer that has seen little progress in meaningful treatment advances.”
KEYNOTE-158 (ClinicalTrials.gov, NCT02628067) is an ongoing global, open-label, non-randomized, multi-cohort, multi-center, Phase 2 study evaluating KEYTRUDA in patients with multiple types of advanced solid tumors – including SCLC – that have progressed on standard of care therapy. The SCLC cohort of the study enrolled 107 patients, regardless of biomarker status, who received KEYTRUDA as monotherapy (200 mg fixed dose every three weeks). The primary endpoint was ORR as evaluated by independent central review using RECIST v1.1. Secondary endpoints are progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety.
In the overall SCLC patient cohort (n=107), data at ASCO showed an ORR of 18.7 percent (95% CI, 11.8-27.4), with a complete response rate of three percent and a partial response rate of 16 percent. Median DOR was not reached (range, 2.1+ to 18.7+ months) and 73 percent of patients had a DOR of 12 months or longer. Median PFS was 2.0 months (95% CI, 1.9-2.1) with six- and 12-month PFS rates of 23.7 percent and 16.8 percent, respectively. Median OS was 8.7 months (95% CI, 5.6-12.0) with six- and 12-month OS rates of 57.5 percent and 40.2 percent, respectively.
In the pre-specified, exploratory analyses based on PD-L1 status, patients whose tumors expressed PD-L1 (n=42) showed an ORR of 35.7 percent (95% CI, 21.6–52.0), with a complete response rate of five percent and a partial response rate of 31 percent. Additionally, median PFS was 2.1 months (95% CI, 2.0-8.1) with six- and 12-month PFS rates of 38.9 percent and 28.5 percent, respectively. Median OS was 14.9 months (95% CI, 5.6-NR) with six- and 12-month OS rates of 66.0 percent and 53.1 percent, respectively.
In patients whose tumors did not express PD-L1 (n=50), ORR was six percent (95% CI, 1.3-16.5), with a complete response rate of two percent and a partial response rate of four percent. Median PFS was 1.9 months (95% CI, 1.6-2.0) with six- and 12-month PFS rates of 14.3 percent and 8.2 percent, respectively. Median OS was 5.9 months (95% CI, 3.3-10.1) with six- and 12-month OS rates of 48.3 percent and 30.7 percent, respectively. In other pre-specified subgroup analyses, the ORR was generally consistent across clinically relevant subgroups, including patients (n=61) who had received two or more prior lines of therapy where the ORR was 23 percent (95% CI, 13.2-35.5).
The safety profile was consistent with what has been seen in previously reported studies of KEYTRUDA monotherapy in lung cancer.