A12 The SHP2 Inhibitor RMC-4630 in Patients with KRAS-Mutant Non-Small Cell Lung Cancer: Preliminary Evaluation of a First-in-Man Phase 1 Clinical Trial
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In a Phase I/II trial of RMC-4630, disease control rate was 71% (5/7), tumor volume reduction in 3 (43%), and one confirmed objective response in KRASG12C mutant NSCLC.
“first clinical data demonstrated a disease control rate of 71% (5/7) with reduction in tumor volume reported in three (43%) and one confirmed objective response in patients with KRASG12C mutant non-small cell lung cancer (38).”
From Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants (2022) · cites this paper as [38]
Pre-clinical models have shown efficacy of RMC-4630 in combination with sotorasib.
“Pre-clinical models have shown efficacy of RMC-4630 in combination with sotorasib57.”
From Selective KRAS G12C inhibitors in non-small cell lung cancer: chemistry, concurrent pathway alterations, and clinical outcomes (2021) · cites this paper as [57]
In a phase I/II study (NCT03634982) with RMC-4630, including patients with tumors harboring RAS alterations, initial clinical data showed a disease control rate of 71% (5/7 patients) with tumor volume reduction in three patients (43%) and a confirmed objective response in one patient with KRASG12C-mutated lung cancer.
“In a phase I/II study (NCT03634982) with RMC-4630, including patients with tumors harboring RAS alterations (including KRAS amplification), initial clinical data showed a disease control rate of 71% (5/7 patients) with tumor volume reduction observed in three patients (43%) and a confirmed objective response in one patient with KRASG12C-mutated lung cancer [61].”
From KRAS, a New Target for Precision Medicine in Colorectal Cancer? (2024) · cites this paper as [61]
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Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants
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SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling
Fedele, C., Li, S., Teng, K. W., Foster, C. J. R., Peng, D., Ran, H., Mita, P., Geer, M. J., Hattori, T., Koide, A., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201414 · Cited by 265 · see citing works
Combinations with Allosteric SHP2 Inhibitor TNO155 to Block Receptor Tyrosine Kinase Signaling
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Drugging KRAS: Current perspectives and state-of-art review
Parikh, K., Banna, G., Liu, S. V., Friedlaender, A., Desai, A., Subbiah, V., & Addeo, A. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01375-4 · Cited by 164 · see citing works
Kerr, D. L., Haderk, F., & Bivona, T. G. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2020.11.007 · Cited by 124 · see citing works
Self-citationA comprehensive review of SHP2 and its role in cancer
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Palma, G., Khurshid, F., Lu, K., Woodward, B., & Husain, H. (2021) · npj Precision Oncology · doi:10.1038/s41698-021-00237-5 · Cited by 72 · see citing works
Santarpia, M., Ciappina, G., Spagnolo, C. C., Squeri, A., Passalacqua, M. I., Aguilar, A., Gonzalez-Cao, M., Giovannetti, E., Silvestris, N., & Rosell, R. (2023) · Translational Lung Cancer Research · doi:10.21037/tlcr-22-639 · Cited by 65 · see citing works
Targeted Degradation of the Oncogenic Phosphatase SHP2
Vemulapalli, V., Donovan, K. A., Seegar, T. C. M., Rogers, J. M., Bae, M., Lumpkin, R. J., Cao, R., Henke, M. T., Ray, S. S., Fischer, E. S., et al. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00377 · Cited by 43 · see citing works
KRAS, a New Target for Precision Medicine in Colorectal Cancer?
Boilève, A., Smolenschi, C., Lambert, A., Boige, V., Delaye, M., Camilleri, G. M., Tarabay, A., Valéry, M., Fuerea, A., Pudlarz, T., et al. (2024) · Cancers · doi:10.3390/cancers16203455 · Cited by 11 · see citing works
- Authors
- Ou, S. I., Koczywas, M., Ulahannan, S., Janne, P., Pacheco, J., Burris, H., McCoach, C., Wang, J. S., Gordon, M., Haura, E., Riess, J. W., Zhu, V., Ng, K., Eckhardt, S. G., Capasso, A., Dua, R., Chen, A., Wang, Z., Hayes, J., Nichols, R., & Bivona, T.
- Affiliations
- City Of Hope National Medical Center (US)
- University of Oklahoma (US)
- Dana-Farber Cancer Institute (US)
- University of Colorado Denver (US)
- Sarah Cannon (US)
- University of California, San Francisco (US)
- HonorHealth (US)
- Moffitt Cancer Center (US)
- University of California, Davis (US)
- University of California, Irvine (US)
- The University of Texas at Austin (US)
- Revolution Medicines (United States) (US)
- ORCID
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 15
- Issue
- 2
- Pages
- S15-S16
- ISSN
- 1556-0864 (ISSN-L)
- OpenAlex
- W3001129149
- Cited by
- 73
- References
- 0
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 14 · 2023: 8 · 2022: 16 · 2021: 13 · 2020: 9
- Type
- conference abstract
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- SHP2 inhibitors, KRAS mutation, non-small cell lung cancer, allosteric inhibition, Ras signaling, receptor tyrosine kinase signaling, oral small-molecule inhibitor
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