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

Author:

Dy Grace K.1ORCID,Govindan Ramaswamy2ORCID,Velcheti Vamsidhar3,Falchook Gerald S.4ORCID,Italiano Antoine5ORCID,Wolf Jürgen6ORCID,Sacher Adrian G.7,Takahashi Toshiaki8ORCID,Ramalingam Suresh S.9ORCID,Dooms Christophe10,Kim Dong-Wan11ORCID,Addeo Alfredo12ORCID,Desai Jayesh13ORCID,Schuler Martin14ORCID,Tomasini Pascale15,Hong David S.16ORCID,Lito Piro17ORCID,Tran Qui18ORCID,Jones Simon18,Anderson Abraham18ORCID,Hindoyan Antreas18,Snyder Wendy18,Skoulidis Ferdinandos16,Li Bob T.17ORCID

Affiliation:

1. Roswell Park Comprehensive Cancer Center, Buffalo, NY

2. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO

3. Perlmutter Cancer Center, New York University Langone, New York, NY

4. Sarah Cannon Research Institute at HealthONE, Denver, CO

5. Institut Bergonie, Bordeaux, France

6. Center for Integrated Oncology, University Hospital Cologne, Cologne, Germany

7. Princess Margaret Cancer Centre, Toronto, Ontario, Canada

8. Shizuoka Cancer Center, Shizuoka, Japan

9. Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA

10. University Hospitals KU Leuven, Leuven, Belgium

11. Seoul National University College of Medicine and Seoul National University Hospital, Seoul, South Korea

12. Hopitaux Universitaires de Geneve, Geneve, Switzerland

13. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

14. West German Cancer Center, University Hospital Essen, Essen, Germany

15. Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, APHM, INSERM, NCRS, CRCM, Hôpital de la Timone, Marseille, France

16. The University of Texas MD Anderson Cancer Center, Houston, TX

17. Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, NY

18. Amgen Inc, Thousand Oaks, CA

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 KRASG12C 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 (ASCO)

Subject

Cancer Research,Oncology

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