Abstract 601P
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.
Resources from the same session
471TiP - A group sequential, response-adaptive randomized double-blinded clinical trial to evaluate add-on olanzapine plus pregabalin to prevent chemotherapy-induced nausea and vomiting (CINV ) in patients belonging to low socio-economic status
Presenter: Mathan Ramasubbu
Session: Poster Display
Resources:
Abstract
472P - Risk of recurrence and optimal adjuvant treatment in invasive lung adenocarcinomas manifesting as radiological part-solid nodules
Presenter: Yang Wo
Session: Poster Display
Resources:
Abstract
473P - Treatment (tx) patterns in resectable stage IA–IIIA non-small cell lung cancer (NSCLC) in China: Subgroup analysis of a global real-world (rw) study
Presenter: Chih-Chi Yang
Session: Poster Display
Resources:
Abstract
474P - The efficacy of image guided coil localisation for surgical resection of undiagnosed solitary lung nodule
Presenter: Jun Rey Leong
Session: Poster Display
Resources:
Abstract
475P - 5-year overall survival and disease free survival outcome between lobectomy and segmentectomy for early stage lung cancer in a mixed Asian population
Presenter: Jianye Chen
Session: Poster Display
Resources:
Abstract
478P - Peri-operative risks in curative lung resection of early stage primary lung cancer patients above 70 years old in a mixed Asian population
Presenter: Ian Goh
Session: Poster Display
Resources:
Abstract
480P - Aumolertinib as adjuvant therapy for resectable stage I-III EGFR-mutant NSCLC: Also effective in EGFR co-mutation
Presenter: Lin Wu
Session: Poster Display
Resources:
Abstract
481P - Comparative analysis of three NGS platforms assessing tumor mutational burden and mutational landscape in resectable non-small cell lung cancer
Presenter: Jii Bum Lee
Session: Poster Display
Resources:
Abstract
482P - Prevalence of EGFR mutations (EGFRm) and its subtypes in patients (pts) with resected stage I-III NSCLC: Results from EARLY-EGFR Singapore cohort
Presenter: Puey Ling Chia
Session: Poster Display
Resources:
Abstract
483P - Genetic profiles and evolutionary trajectory of early stage lung adenocarcinoma (AAH, AIS, MIA and IAC) revealed by multiplex sequecing
Presenter: lixuan lin
Session: Poster Display
Resources:
Abstract