Overall survival and exploratory subgroup analyses from the phase 2 CodeBreaK 100 trial evaluating sotorasib in pretreated KRAS p.G12C mutated non-small cell lung cancer.
Abstract
9003 Background: In the registrational phase 2 CodeBreaK 100 trial, sotorasib demonstrated an objective response rate (ORR) of 37.1% (95% Cl: 28.6, 46.2) and a median progression-free survival (PFS) of 6.8 months (95% Cl: 5.1, 8.2) in patients with pretreated KRAS p.G12C mutated non-small cell lung cancer (NSCLC). Tumor response was observed in patients bearing co-mutations in STK11, a driver of poor clinical outcomes with standard of care. Here, we report efficacy across an extended set of patient subgroups by key baseline characteristics and biomarkers. Methods: Sotorasib was given orally at 960 mg once daily to eligible patients who had advanced NSCLC harboring KRAS p.G12C and received prior standard therapies. Primary endpoint was ORR assessed by central review. Key secondary endpoints included PFS, overall survival, and safety. KRAS p.G12C mutant allele frequency (MAF) and tumor mutational burden (TMB) were analyzed by next-generation sequencing (NGS) using tissue samples. Mutational status of individual genes was determined by NGS using tissue and/or plasma samples. Correlations between response and KRAS p.G12C MAF, TMB, or co-mutations were analyzed in subsets of patients who had available respective results. Association between MAF and response was reported by odds ratio (95% CI), from a logistic regression with dependent variable of log odds of being a responder and an independent variable of MAF in a unit of 10%. Results: ORR across subgroups is presented in the Table. Response was independent of KRAS p.G12C MAF in the study population (odds ratio [95% CI]: 1.11 [0.88, 1.39]). OS remained immature. Conclusions: In the exploratory analyses of the phase 2 CodeBreaK 100 trial, the clinical benefit of sotorasib was observed across patient subgroups. Overall survival and updated exploratory analyses will be presented. Clinical trial information: NCT03600883. [Table: see text]
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Subgroup analyses demonstrated consistency of benefit for both overall response and overall survival across various subgroups including prior lines of therapy and prior treatment history.
“Subgroup analyses demonstrated consistency of benefit for both overall response and overall survival across various subgroups including prior lines of therapy and prior treatment history33.”
From Selective KRAS G12C inhibitors in non-small cell lung cancer: chemistry, concurrent pathway alterations, and clinical outcomes (2021) · cites this paper as [33]
Biomarkers such as PD-L1 and TMB were not predictive or prognostic in patients with KRAS G12C-mutant NSCLC in CodeBreaK100.
“Biomarkers such as PD-L1 and TMB, which have been studied to predict outcomes with immune checkpoint inhibitors, were not predictive or prognostic in patients with KRAS G12C-mutant NSCLC in CodeBreaK100 [104].”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [104]
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Blair, H. A. (2021) · Drugs · doi:10.1007/s40265-021-01574-2 · Cited by 241 · see citing works
KRASG12C-independent feedback activation of wild-type RAS constrains KRASG12C inhibitor efficacy
Ryan, M. B., Coker, O., Sorokin, A., Fella, K., Barnes, H., Wong, E., Kanikarla, P., Gao, F., Zhang, Y., Zhou, L., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110993 · Cited by 177 · see citing works
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
Self-citationPalma, 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
- Authors
- Skoulidis, F., Li, B. T., Govindan, R., Dy, G. K., Shapiro, G., Bauml, J., Schuler, M. H., Addeo, A., Kato, T., Besse, B., Anderson, A., Ang, A., Ngarmchamnanrith, G., Tran, Q., & Velcheti, V.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Washington University in St. Louis (US)
- Roswell Park Comprehensive Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- University of Pennsylvania (US)
- West German Cancer Centre, University Hospital Essen, Essen, Germany;
- University Hospital of Geneva (CH)
- Kanagawa Cancer Center (JP)
- Institut Gustave Roussy (FR)
- Amgen (United States) (US)
- NYU Langone Health (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2021-05-20
- Volume
- 39
- Issue
- 15_suppl
- Pages
- 9003-9003
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W3167020670
- Cited by
- 24
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 5 · 2022: 5 · 2021: 9
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Funders
- Amgen Inc
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- sotorasib, non-small cell lung cancer, overall survival, objective response rate, tumor mutational burden, predictive biomarkers, subgroup analysis, KRAS inhibitors
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