Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Clinical Studies

Efficacy and safety of garsorasib in patients with KRAS G12C-mutated advanced pancreatic cancer

British Journal of Cancer volume 134, pages 457–462 (2026)Cite this article

Subjects

Abstract

Background

Garsorasib (D-1553), a highly selective, oral KRASG12C inhibitor, has shown clinical efficacy in NSCLC and CRC and is under evaluation in pancreatic cancer.

Methods

Pancreatic cancer patients with KRAS G12C mutation were enroled and received garsorasib 600 mg twice daily treatment in two international, multicenter, open-label phase 1/2 trials (NCT04585035 and NCT05383898) with similar eligibility criteria. Their data were pooled for analyses of efficacy and safety endpoints.

Results

As of April 30, 2024, 24 KRAS G12C–mutated pancreatic cancer patients were enroled with a median follow-up of 8.9 months (range 1.1–22.9). Among 22 evaluable patients, the confirmed objective response rate (ORR) was 45.5% (95% CI, 24.4 to 67.8) with a median duration of response (DOR) of 6.4 months (95% CI, 4.2 to 16.4). The median progression-free survival (PFS) was 7.6 months (95% CI, 3.3 to 8.5) and the 6-month OS rate was 79.2% (95% CI, 57.0, 90.8). Treatment-related adverse events (TRAEs) occurred in 18 (75.0%) patients, including 6 (25.0%) with grade ≥3 events. No TRAEs led to treatment discontinuation. The safety profile was consistent with previous reports of garsorasib.

Conclusion

Garsorasib demonstrated encouraging antitumor activity and a tolerable safety profile in patients with KRAS G12C-mutated advanced pancreatic cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2: Efficacy outcomes with garsorasib in KRAS G12C-mutated pancreatic cancer.

Similar content being viewed by others

Data availability

InventisBio will honor legitimate requests for clinical trial data from qualified researchers, upon request, as necessary for conducting clinically meaningful and GCP compliant research. InventisBio will provide completed clinical trial data to be posted on the clinicaltrials.gov registry for products or indications that have been approved by regulators. In general, data will be made available for request approximately 12 months after clinical trial completion.

References

  1. Bray, F, Laversanne, M, Sung, H, Ferlay, J, Siegel, RL, Soerjomataram, I et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2004. https://doi.org/10.3322/caac.21834.

  2. Hu ZI, O’Reilly EM. Therapeutic developments in pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2024;21:7–24.

    Article  PubMed  Google Scholar 

  3. Chen X, Zeh HJ, Kang R, Kroemer G, Tang D. Cell death in pancreatic cancer: from pathogenesis to therapy. Nat Rev Gastroenterol Hepatol. 2021;18:804–23.

    Article  PubMed  Google Scholar 

  4. Raphael MJ, Raskin W, Habbous S, Tai X, Beca J, Dai WF, et al. The Association of Drug-Funding Reimbursement with survival outcomes and use of new systemic therapies among patients with advanced pancreatic cancer. JAMA Netw Open. 2021;4:e2133388.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.

    Article  CAS  PubMed  Google Scholar 

  6. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.

    Article  Google Scholar 

  7. Witkiewicz AK, McMillan EA, Balaji U, Baek G, Lin WC, Mansour J, et al. Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nat Commun. 2015;6:6744.

    Article  CAS  PubMed  Google Scholar 

  8. Luo J. KRAS mutation in pancreatic cancer. Semin Oncol. 2021;48:10–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bekaii-Saab TS, Yaeger R, Spira AI, Pelster MS, Sabari JK, Hafez N, et al. Adagrasib in advanced solid tumors harboring a KRAS(G12C) mutation. J Clin Oncol. 2023;41:4097–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, et al. Sotorasib in KRAS p.G12C-mutated advanced pancreatic cancer. N Engl J Med. 2023;388:33–43.

    Article  CAS  PubMed  Google Scholar 

  11. Li J, Shen L, Gu Y, Calles A, Wu L, Ba Y, et al. Preliminary activity and safety results of KRAS G12C inhibitor glecirasib (JAB-21822) in patients with pancreatic cancer and other solid tumors. J Clin Oncol. 2024;42:604.

    Article  CAS  Google Scholar 

  12. Shi Z, Weng J, Niu H, Yang H, Liu R, Weng Y, et al. D-1553: A novel KRAS(G12C) inhibitor with potent and selective cellular and in vivo antitumor activity. Cancer Sci. 2023;114:2951–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li Z, Song Z, Zhao Y, Wang P, Jiang L, Gong Y, et al. D-1553 (Garsorasib), a potent and selective inhibitor of KRAS(G12C) in patients with NSCLC: phase 1 study results. J Thorac Oncol. 2023;18:940–51.

    Article  CAS  PubMed  Google Scholar 

  14. Ruan D-y, Lee MA, Deng Y, Lee K-W, Millward M, Grewal JS, et al. Safety and efficacy of D-1553 in KRAS G12C-mutated colorectal cancer: results from a phase I/II study. J Clin Oncol. 2023;41:3563.

    Article  Google Scholar 

  15. Xu RH, Xu Y, Yan D, Munster P, Ruan D, Deng Y, et al. 550O Safety and efficacy of D-1553 in combination with cetuximab in KRAS G12C mutated colorectal cancer (CRC): a phase II study. Ann Oncol. 2023;34:S410–S1.

    Article  Google Scholar 

  16. Kondo S, Yan D, Ganju V, Richardson G, Hou X, Shan J, et al. 1622P D-1553 in patients with KRAS G12C mutated advanced pancreatic cancer (PCA). Ann Oncol. 2023;34:S898–S899.

    Article  Google Scholar 

  17. Li Z, Dang X, Huang D, Jin S, Li W, Shi J, et al. Abstract CT246: Open-label, single-arm, multicenter, phase 2 trial of garsorasib in KRAS G12C-mutated non-small-cell lung cancer. Cancer Res. 2024;84:CT246.

    Article  Google Scholar 

  18. Wang-Gillam A, Hubner RA, Siveke JT, Von Hoff DD, Belanger B, de Jong FA, et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 2019;108:78–87.

    Article  CAS  PubMed  Google Scholar 

  19. Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014;32:2423–9.

    Article  CAS  PubMed  Google Scholar 

  20. Gill S, Ko YJ, Cripps C, Beaudoin A, Dhesy-Thind S, Zulfiqar M, et al. PANCREOX: a randomized phase III study of fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol. 2016;34:3914–20.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the patients and their families, clinical staff, and the collaborators who contributed to this study. Medical writing assistance for this manuscript was provided by Yihong Zhang and Xinying Liu from InventisBio.

Funding

The study was sponsored by InventisBio Co., Ltd.

Author information

Authors and Affiliations

  1. National Cancer Center Hospital, Tokyo, Japan

    Noboru Yamamoto

  2. Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China

    Dong Yan

  3. Peninsula and Southeast Haematology and Oncology Group, Frankston, Australia

    Vinod Ganju

  4. Henan Cancer Hospital, Zhengzhou, China

    Xinfang Hou

  5. Sir Run Run Shaw Hospital (SRRSH), affiliated with the Zhejiang University School of Medicine, Hangzhou, China

    Hongming Pan

  6. The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

    Jianzhen Shan

  7. Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Liwei Wang

  8. Asan Medical Center, Seoul, South Korea

    Sang-We Kim

  9. Cabrini Hospital - Malvern, Malvern, VIC, Australia

    Gary Richardson

  10. Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA

    Rachel E. Sanborn

  11. Liaoning Cancer Hospital and Institute, Shenyang, China

    Jingdong Zhang

  12. InventisBio Co., Ltd., Shanghai, China

    Ziyong Xiang, Wenjia Wang, Zhe Shi, Ling Zhang & Yaolin Wang

  13. Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, China

    Rui-Hua Xu

  14. Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China

    Rui-Hua Xu

Authors
  1. Noboru Yamamoto
    View author publications

    Search author on:PubMed Google Scholar

  2. Dong Yan
    View author publications

    Search author on:PubMed Google Scholar

  3. Vinod Ganju
    View author publications

    Search author on:PubMed Google Scholar

  4. Xinfang Hou
    View author publications

    Search author on:PubMed Google Scholar

  5. Hongming Pan
    View author publications

    Search author on:PubMed Google Scholar

  6. Jianzhen Shan
    View author publications

    Search author on:PubMed Google Scholar

  7. Liwei Wang
    View author publications

    Search author on:PubMed Google Scholar

  8. Sang-We Kim
    View author publications

    Search author on:PubMed Google Scholar

  9. Gary Richardson
    View author publications

    Search author on:PubMed Google Scholar

  10. Rachel E. Sanborn
    View author publications

    Search author on:PubMed Google Scholar

  11. Jingdong Zhang
    View author publications

    Search author on:PubMed Google Scholar

  12. Ziyong Xiang
    View author publications

    Search author on:PubMed Google Scholar

  13. Wenjia Wang
    View author publications

    Search author on:PubMed Google Scholar

  14. Zhe Shi
    View author publications

    Search author on:PubMed Google Scholar

  15. Ling Zhang
    View author publications

    Search author on:PubMed Google Scholar

  16. Yaolin Wang
    View author publications

    Search author on:PubMed Google Scholar

  17. Rui-Hua Xu
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Conceptualization and Methodology: NY, ZX, WW, ZS, LZ, YW, R-HX. Investigation: NY, DY, VG, XH, HP, JS, LW, SK, GR, RES, JZ, R-HX. Writing original draft: NY, ZX, WW, ZS, LZ, R-HX. Writing, review and editing: NY, DY, VG, XH, HP, JS, LW, SK, GR, RES, JZ, ZX, WW, ZS, LZ, YW, R-HX. Supervision: ZS, LZ, YW. Project administration: ZX, WW.

Corresponding author

Correspondence to Rui-Hua Xu.

Ethics declarations

Competing interests

NY reports honoraria from Chugai Pharma, Daiichi Sankyo/UCB Japan, Eisai, reports consulting or advisory fees from Eisai, Boehringer Ingelheim, CMIC, Chugai Pharma, Healios, Merck, Mitsubishi Tanabe, Rakuten Medical Japan, Noile-Immune Biotech, Inc, reports research funding from Chugai Pharma, Taiho Pharmaceutical, Eisai, Astellas Pharma, Novartis, Daiichi Sankyo, Lilly Japan, Boehringer Ingelheim, Takeda, Kyowa Hakko Kirin, Bayer, Pfizer, Ono Pharmaceutical, Janssen, MSD, AbbVie, Bristol Myers Squibb, Merck Serono, GlaxoSmithKline, Sumitomo Dainippon, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab/Seattle Genetics, Shionogi, Toray Industries, Kaken Pharmaceutical, AstraZeneca, CMIC, InventisBio, Rakuten Medical, Amgen, Bicycle Therapeutics. RES reports grants or contracts from AstraZeneca and Merck; reports consulting fees from GlaxoSmithKline, AstraZeneca, Janssen Oncology, Macrogenics, Daiichi, Sanofi, BeiGene, Gilead, Regeneron, Targeted Oncology, G1 Therapeutics, GE HealthCare, Amgen, and Lilly Oncology; reports payment or honoraria for lectures, presentations from EMD Serono, Illumina, GameOn!, OncLive, Binay Foundation, APP Oncology, and Masters in Thoracic Oncology Summit; participates on advisory board for GlaxoSmithKline, AstraZeneca, Janssen Oncology, Macrogenics, Daiichi, Sanofi, BeiGene, Gilead, Regeneron, Targeted Oncology, G1 Therapeutics, GE HealthCare, Amgen, and Lilly Oncology. ZX, WW, ZS, LZ, YW reports InventisBio employment and stock. R-HX reports speaker fees from Bristol Myers Squibb, Roche, MerckSerono, Hutchison, Hengrui, Junshi, Qilu, CPPC, Henlius, and participates on advisory board for Astellas, MSD, AstraZeneca, Junshi, Hengrui, BeiGene. Innovent, CPPC, and Keymed. All other authors declare no competing interests.

Ethics approval and consent to participate

The studies were conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and were approved by the ethics committee of Sun Yat-sen University Cancer Center, and by the ethics committees of the other participating sites. Written informed consent was obtained from all patients prior to screening.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamamoto, N., Yan, D., Ganju, V. et al. Efficacy and safety of garsorasib in patients with KRAS G12C-mutated advanced pancreatic cancer. Br J Cancer 134, 457–462 (2026). https://doi.org/10.1038/s41416-025-03286-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41416-025-03286-w

Search

Advanced search

Quick links