KEY TAKEAWAYS
- The KEYNOTE-158 phase 2 trial aimed to investigate the efficacy and safety of pembro in Chinese descent patients with MSI-H/dMMR tumors.
- The primary endpoint was to determine ORR.
- Researchers noticed that pembro demonstrated clinically meaningful antitumor activity and durable responses in Chinese patients with MSI-H/dMMR tumors.
The multicohort KEYNOTE-158 trial played a pivotal role in securing regulatory approvals from the US FDA and EMA for pembrolizumab (pembro) in treating microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors. Notably, the incidence of microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) advanced cancer among patients of Chinese descent aligns with Western populations, as evidenced by (Liu et al 2019, Cancer Research 79:616).
In the specific context of Cohort L within KEYNOTE-158, Xiaohua Wu and his team’s evaluation focused on assessing the efficacy and safety of pembro in individuals of Chinese descent diagnosed with MSI-H/dMMR solid tumors.
They performed an inclusive analysis in a nonrandomized, phase 2, open-label trial involving Chinese patients ≥ 18 years. Enrollees were required to be of Chinese descent, with confirmed MSI-H/dMMR unresectable or metastatic cancers, and had received ≥1 prior line of therapy. Eligible patients were administered 200 mg pembro every 3 weeks for up to 35 cycles until disease progression, unacceptable toxicity, or patient/investigator withdrawal.
The MSI-H/dMMR status of participants was centrally assessed using polymerase chain reaction (PCR) or immunohistochemistry (IHC). The primary endpoint centered on the objective response rate (ORR) per RECIST 1.1 through an independent central review. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety assessments. The database cut-off date for this analysis was July 26, 2022.
About 24 patients were enrolled in this study as of the data cut-off, with 20 undergoing efficacy evaluation having at least 6 months of follow-up. The overall ORR for these 20 patients was 70.0% (95% CI: 45.7%-88.1%). The median DOR was not reached (NR) within a (range of 2.1+ to 19.3+), accompanied by a 12-month DOR rate of 85.7%.
Median PFS was also NR with a (95% CI: 15.8-NR) and an 18-month PFS rate of 68.0%. The median OS was NR (95% CI: 9.5, NR), and an 18-month OS rate of 80.2%.
Treatment-related adverse events (AE) were reported in 19 (79%) of the 24 enrolled patients. Grade ≥3 treatment-related AEs occurred in 4 (17%) pts; notably, there were no grade 5 AEs. Immune-mediated AEs were observed in 8 pts (33%), with 2 patients (8%) experiencing grade 3 AEs (myositis or rash in 1 patient each). Importantly, no grade 4 or 5 immune-mediated AEs were reported in the study.
The study concluded that pembro demonstrated clinically meaningful antitumor activity and durable responses in patients of Chinese descent with MSI-H/dMMR tumors. The safety profile was manageable, and no new safety signals emerged. These findings align consistently with results reported for patients in the global population, underscoring pembro’s potential efficacy and safety in this demographic.
The study is sponsored by Merck Sharp & Dohme LLC
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/78
Clinical Trial: https://clinicaltrials.gov/study/NCT02628067
Wu X, Mao Y, Xu N, et al. (2023). “Pembrolizumab in patients of Chinese descent with microsatellite instability-high/mismatch repair deficient advanced solid tumors: KEYNOTE-158.” Presented at ESMO ASIA 2023 (Abstract 601P).
