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

Authors

Grace K Dy
Ramaswamy Govindan
Vamsidhar Velcheti
Gerald S Falchook
Antoine Italiano
Jürgen Wolf
Adrian G Sacher
Toshiaki Takahashi
Suresh S Ramalingam
Christophe Dooms
Dong-Wan Kim
Alfredo Addeo
Jayesh Desai
Martin Schuler
Pascale Tomasini
David S Hong
Piro Lito
Qui Tran
Simon Jones
Abraham Anderson
Antreas Hindoyan
Wendy Snyder
Ferdinandos Skoulidis
Bob T Li

Publication Date

6-20-2023

Journal

Journal of Clinical Oncology

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.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Kelch-Like ECH-Associated Protein 1, Lung Neoplasms, NF-E2-Related Factor 2, Proto-Oncogene Proteins p21(ras)

DOI

10.1200/JCO.22.02524

PMID

37098232

PMCID

PMC10414711

PubMedCentral® Posted Date

4-25-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes