KEYNOTE-158: Final analysis of pembrolizumab in patients of Chinese descent with microsatellite instability-high/mismatch repair deficient advanced solid tumors.

e15137 Background: The multicohort non-randomized, phase 2 KEYNOTE-158 (NCT02628067) trial supported the FDA approval of pembrolizumab for unresectable or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) solid tumors. Incidence of advanced MSI-H/dMMR tumors in patients (pts) of Chinese descent is similar to that in Western populations. In KEYNOTE-158 cohort L, we evaluated the antitumor activity of pembrolizumab in pts of Chinese descent with MSI-H/dMMR solid tumors. We previously reported an ORR of 70% in 20 pts from cohort L. Here we present results of the final analysis for 30 pts with 18 months (mo) of follow up. Methods: Eligible pts of Chinese descent from China aged ≥18 years were enrolled. Pts had to have confirmed unresectable or metastatic MSI-H/dMMR tumors, and ≥1 prior lines of therapy. Pts received 200 mg pembrolizumab Q3W for up to 35 cycles, until progression, unacceptable toxicity, or pt/investigator withdrawal. MSI-H/dMMR status was assessed centrally by PCR and IHC. The primary endpoint was ORR per RECIST 1.1 by central review. Secondary endpoints were DOR, PFS, OS and safety. The database cut-off date was May 5, 2023. Results: A total of 30 pts were enrolled; 7 (23%) were aged ≥65 years, and 20 (67%) were female. At data cut-off, 14 (47%) pts discontinued treatment; 12 (40%) due to progressive disease, 1 (3%) due to adverse events (AE), and 1 (3%) due to physician decision. The median follow-up (range) was 18.0 mo (6.4 – 32.7). The ORR was 66.7% (6 CR; 14 PR [95% CI: 47.2%- 82.7%]). The median DOR was not reached (NR) (range, 1.8+ - 29.5+) with a 12-mo DOR rate of 85.9%. Median PFS was NR (95% CI: 8.1-NR) with an 18-mo PFS rate of 63.0%. The median OS was NR (95% CI: 19.1, NR) with an 18-mo OS rate of 78.8%. Treatment-related AEs were reported in 22 (73%) pts. Grade 3-4 treatment-related AEs occurred in 7 (23%) pts. There were no grade 5 AEs. Immune-mediated AEs occurred in 11 pts (37%); 2 (7%) had grade 3 AEs (myositis or rash in 1 pt each). No grade 4-5 immune-mediated AEs occurred. Conclusions: Pembrolizumab continues to provide clinically meaningful antitumor activity and durable responses with a manageable safety profile in pts of Chinese descent with MSI-H/dMMR tumors. No new safety signals were identified. These results are consistent with those reported in the global population and further support the use of pembrolizumab in pts of Chinese descent with MSI-H/dMMR tumors. Clinical trial information: NCT02628067 .