Garsorasib (D-1553) in Combination With Pembrolizumab and Chemotherapy for First-Line Metastatic NSCLC With KRAS G12C Mutation: Results of a Phase 1b Study.
10 affiliations
- 1Department of Oncology, Beijing Luhe Hospital, Capital Medical University, Beijing, People's Republic of China.
- 2Department of Oncology, Wuxi People's Hospital, Nanjing Medical University, Wuxi, People's Republic of China.
- 3Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Henan, People's Republic of China.
- 4Department of Medical Oncology, St. Vincent's Hospital, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
- 5Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
- 6Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon.
- 7Division of Hematology/Oncology, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan.
- 8Linear Clinical Research, Ltd., and School of Medicine, University of Western Australia, Perth, West Australia, Australia.
- 9InventisBio Co., Ltd., Shanghai, People's Republic of China.
- 10Merck & Co., Inc., Rahway, NJ, USA.
Abstract
Introduction
Garsorasib (D-1553) is an orally administered selective KRAS G12C inhibitor. We report results from group 1 of the phase 1b D1553-101 study assessing garsorasib plus pembrolizumab and platinum-based chemotherapy in participants with KRAS G12C-mutated advanced or metastatic NSCLC.Methods
Eligible participants had locally advanced or metastatic NSCLC with KRAS G12C mutation and were candidates for pembrolizumab plus platinum-based chemotherapy. Participants received garsorasib 600 mg once daily or twice daily combined with pembrolizumab 200 mg once every 3 weeks plus 4 to 6 cycles of cisplatin or carboplatin and pemetrexed (nonsquamous histology) or carboplatin and paclitaxel (squamous histology). The primary end points were safety and the incidence of dose-limiting toxicities (DLTs).Results
As of February 24, 2024, 17 participants received garsorasib 600 mg once daily (n = 10) or twice daily (n = 7) combined with pembrolizumab plus platinum-based chemotherapy. Overall, 94% of participants experienced grade 3 or higher treatment-related adverse events (AEs), and 88% had a dose reduction or interruption due to treatment-related AEs. One participant in the twice-daily group experienced a DLT of grade 2 diarrhea; no other DLTs occurred. Among all participants, the objective response rate was 59%, and the median progression-free survival was 7.4 months.Conclusion
In participants with KRAS G12C-mutated locally advanced or metastatic NSCLC, despite an encouraging signal of efficacy, the incidence of treatment-related AEs with garsorasib plus pembrolizumab and platinum-based chemotherapy was high, and participants frequently had dose modifications or interruptions due to treatment-related AEs. Based on these findings, the study did not proceed to phase 2.Clinicaltrialsgov identifier
NCT04585035.
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BibTeX
@article{yan2026garsorasib,
title = {{Garsorasib (D-1553) in Combination With Pembrolizumab and Chemotherapy for First-Line Metastatic NSCLC With KRAS G12C Mutation: Results of a Phase 1b Study.}},
author = {Dong Yan and Chaoying Liu and Xingya Li and Melissa Moore and Ruihua Xu and Rachel E Sanborn and Shirish M Gadgeel and Michael Millward and Zhe Shi and Yaolin Wang and Kathryn Stazzone and Michael J Chisamore and Ling Zhang},
journal = {JTO clinical and research reports},
year = {2026},
month = jun,
doi = {10.1016/j.jtocrr.2026.101037},
url = {https://europepmc.org/article/MED/42924167},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Garsorasib (D-1553) in Combination With Pembrolizumab and Chemotherapy for First-Line Metastatic NSCLC With KRAS G12C Mutation: Results of a Phase 1b Study.
AU - Dong Yan
AU - Chaoying Liu
AU - Xingya Li
AU - Melissa Moore
AU - Ruihua Xu
AU - Rachel E Sanborn
AU - Shirish M Gadgeel
AU - Michael Millward
AU - Zhe Shi
AU - Yaolin Wang
AU - Kathryn Stazzone
AU - Michael J Chisamore
AU - Ling Zhang
PY - 2026
DA - 2026/06/30
JO - JTO clinical and research reports
DO - 10.1016/j.jtocrr.2026.101037
UR - https://europepmc.org/article/MED/42924167
AB - Introduction Garsorasib (D-1553) is an orally administered selective KRAS G12C inhibitor. We report results from group 1 of the phase 1b D1553-101 study assessing garsorasib plus pembrolizumab and platinum-based chemotherapy in participants with KRAS G12C-mutated advanced or metastatic NSCLC.Methods Eligible participants had locally advanced or metastatic NSCLC with KRAS G12C mutation and were candidates for pembrolizumab plus platinum-based chemotherapy. Participants received garsorasib 600 mg once daily or twice daily combined with pembrolizumab 200 mg once every 3 weeks plus 4 to 6 cycles of cisplatin or carboplatin and pemetrexed (nonsquamous histology) or carboplatin and paclitaxel (squamous histology). The primary end points were safety and the incidence of dose-limiting toxicities (DLTs).Results As of February 24, 2024, 17 participants received garsorasib 600 mg once daily (n = 10) or twice daily (n = 7) combined with pembrolizumab plus platinum-based chemotherapy. Overall, 94% of participants experienced grade 3 or higher treatment-related adverse events (AEs), and 88% had a dose reduction or interruption due to treatment-related AEs. One participant in the twice-daily group experienced a DLT of grade 2 diarrhea; no other DLTs occurred. Among all participants, the objective response rate was 59%, and the median progression-free survival was 7.4 months.Conclusion In participants with KRAS G12C-mutated locally advanced or metastatic NSCLC, despite an encouraging signal of efficacy, the incidence of treatment-related AEs with garsorasib plus pembrolizumab and platinum-based chemotherapy was high, and participants frequently had dose modifications or interruptions due to treatment-related AEs. Based on these findings, the study did not proceed to phase 2.Clinicaltrialsgov identifier NCT04585035.
SN - 2666-3643
ER -