Genentech Oncology
Divarasib (KRAS G12C inhibitor)
(RG6330)
Solid Tumor
Phase I
A Study to Evaluate the Safety, Pharmacokinetics, and Activity of divarasib in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation
NCT04449874
Lung
Phase III
A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)
NCT03178552
Phase II
A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)
NCT03178552
Phase I
A Study to Evaluate the Safety, Pharmacokinetics, and Activity of divarasib Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation
NCT04449874
Gastrointestinal
Phase I
A Study to Evaluate the Safety, Pharmacokinetics, and Activity of Divarasib Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation
NCT04449874
A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
NCT04929223
This compound and its uses are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should be not construed as a recommendation for use. The relevance of findings in preclinical studies to humans is currently being evaluated.
Designed to inhibit the KRAS G12C mutant protein and lock it in its inactive state
Divarasib is an orally available small molecule, and in preclinical models showed potent and selective inhibition of the KRAS G12C protein.1
By locking the mutant KRAS G12C into its inactive GDP-bound state, divarasib turns off oncogenic signaling in preclinical models.
Divarasib is designed to selectively bind to the switch II pocket of KRAS G12C protein through a specific interaction with the cysteine residue at position 12, and irreversibly lock it in the inactive GDP-bound state.1
In preclinical models, the combination of KRAS G12C inhibitors with other agents demonstrated synergistic anti-tumor activity.2,3
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Purkey H. ND11 - discovery of GDC-6036, a clinical stage treatment for KRAS G12C-positive cancers. Abstract presented at: Proceedings of the 113th Annual Meeting of the American Association for Cancer Research; April 8-13, 2022; New Orleans, LA. Abstract nr ND11.
Purkey H. ND11 - discovery of GDC-6036, a clinical stage treatment for KRAS G12C-positive cancers. Abstract presented at: Proceedings of the 113th Annual Meeting of the American Association for Cancer Research; April 8-13, 2022; New Orleans, LA. Abstract nr ND11.
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Huang L, Guo Z, Wang F, Fu L. KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther. 2021;6(1):386. PMID: 34776511
Huang L, Guo Z, Wang F, Fu L. KRAS mutation: from undruggable to druggable in cancer. Signal Transduct Target Ther. 2021;6(1):386. PMID: 34776511
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Williams B, Taylor A, Orozco O, et al. Discovery and characterization of the potent, allosteric SHP2 inhibitor GDC-1971 for the treatment of RTK/RAS driven tumors. Abstract presented at: Proceedings of the 113th Annual Meeting of the American Association for Cancer Research; April 8-13, 2022; New Orleans, LA. Abstract nr 3327.
Williams B, Taylor A, Orozco O, et al. Discovery and characterization of the potent, allosteric SHP2 inhibitor GDC-1971 for the treatment of RTK/RAS driven tumors. Abstract presented at: Proceedings of the 113th Annual Meeting of the American Association for Cancer Research; April 8-13, 2022; New Orleans, LA. Abstract nr 3327.
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