Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100

Dy, GK; Govindan, R; Velcheti, V; Falchook, GS; Italiano, A; Wolf, J; Sacher, AG; Takahashi, T; Ramalingam, SS; Dooms, C; Kim, DW; Addeo, A; Desai, J; Schuler, M; Tomasini, P; Hong, DS; Lito, P; Tran, Q; Jones, S; Anderson, A; Hindoyan, A; Snyder, W; Skoulidis, F; Li, BT

Author(s): Dy, GK; Govindan, R; Velcheti, V; Falchook, GS; Italiano, A; Wolf, J; Sacher, AG; Takahashi, T; Ramalingam, SS; Dooms, C; Kim, DW; Addeo, A; Desai, J; Schuler, M; Tomasini, P; Hong, DS; Lito, P; Tran, Q; Jones, S; Anderson, A; Hindoyan, A; Snyder, W; Skoulidis, F; Li, BT;
Details: Publication Year 2023-06-20,Volume 41,Issue #18,Page 3311-3317
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In the longest follow-up, to our knowledge, for a KRAS(G12C) inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with KRAS G12C-mutated advanced non-small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical trial (ClinicalTrials.gov identifier: NCT03600883). This multicenter, single-group, open-label phase I/phase II trial enrolled 174 patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC after progression on prior therapies. Patients (N = 174) received sotorasib 960 mg once daily with the primary end points for phase I of safety and tolerability and for phase II of objective response rate (ORR). Sotorasib produced an ORR of 41%, median duration of response of 12.3 months, progression-free survival (PFS) of 6.3 months, overall survival (OS) of 12.5 months, and 2-year OS rate of 33%. Long-term clinical benefit (PFS >/= 12 months) was observed in 40 (23%) patients across PD-L1 expression levels, in a proportion of patients with somatic STK11 and/or KEAP1 alterations, and was associated with lower baseline circulating tumor DNA levels. Sotorasib was well tolerated, with few late-onset treatment-related toxicities, none of which led to treatment discontinuation. These results demonstrate the long-term benefit of sotorasib, including in subgroups with poor prognosis.
Publisher: American Society of Clinical Oncology
Keywords: Humans; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics; Kelch-Like ECH-Associated Protein 1; *Lung Neoplasms/drug therapy/genetics; NF-E2-Related Factor 2; Proto-Oncogene Proteins p21(ras)/genetics
Department(s): Medical Oncology
PubMed ID: 37098232
Publisher's Version: https://doi.org/10.1200/JCO.22.02524
Open Access at Publisher's Site: https://doi.org/10.1200/jco.22.02524
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-09-14 03:09:10

Last Modified: 2023-09-14 03:09:44