601P - Pembrolizumab in patients of Chinese descent with microsatellite instability-high/mismatch repair deficient advanced solid tumors: KEYNOTE-158

Background

The multicohort KEYNOTE-158 (NCT02628067) trial supported the US FDA and EMA approval of pembrolizumab across multiple microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors. The incidence of MSI-H/dMMR advanced cancer in patients (pts) of Chinese descent is similar to that reported in Western populations (Liu et al 2019, Cancer Research 79:616). In cohort L of KEYNOTE-158, we evaluated the efficacy and safety of pembrolizumab in pts of Chinese descent with MSI-H/dMMR solid tumors.

Methods

In this nonrandomized, phase 2, open-label trial, pts aged ≥ 18 years of Chinese descent were enrolled. These pts had to have confirmed MSI-H/dMMR unresectable or metastatic cancers who had ≥1 prior lines of therapy. Eligible 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 or ICH. The primary endpoint was ORR per RECIST 1.1 by independent central review. Secondary endpoints were DOR, PFS, OS and safety. The database cut-off date was July 26, 2022.

Results

At data cut-off, a total of 24 pts were enrolled of which 20 pts were for efficacy evaluation having at least 6 months (mo) of follow-up. The overall ORR was 70.0% (95% CI: 45.7%- 88.1%) for the 20 pts. The median DOR was not reached (NR) (range, 2.1+ - 19.3+) with a 12-mo DOR rate of 85.7%. Median PFS was NR (95% CI: 15.8-NR) with an 18-mo PFS rate of 68.0%. The median OS was NR (95% CI: 9.5, NR) with an 18-mo OS rate of 80.2%. Treatment-related adverse events (AE) were reported in 19 (79%) of the 24 pts enrolled. Grade ≥3 treatment-related AEs occurred in 4 (17%) pts with no grade 5 AEs. Immune-mediated AEs occurred in 8 pts (33%). Of these pts, 2 (8%) had grade 3 AEs (myositis or rash in 1 pt each). No grade 4 or 5 immune-mediated AEs occurred.

Conclusions

Pembrolizumab provided clinically meaningful antitumor activity and durable responses in pts of Chinese descent with MSI-H/dMMR tumors, with a manageable safety profile. No new safety signals were identified. These results are consistent with those reported for patients in the global population.

Clinical trial identification

NCT02628067; first posted December 9, 2015.

Editorial acknowledgement

Provided by Jose Casasnovas Nieves, PhD, an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

M. Xu, N. Li, Y. Mao: Financial Interests, Personal, Full or part-time Employment: MSD China. A. Gozman: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. All other authors have declared no conflicts of interest.