Dr Goldberg on the Investigation of VIC-1911 With/Without Sotorasib in KRAS G12C-Mutant NSCLC

Sarah Goldberg, MD, MPH, associate professor, medical oncology, associate director, Medical Oncology-Hematology Program, research director, Center for Thoracic Cancers, chief, Thoracic Oncology, Yale School of Medicine, thoracic oncologist, Yale Cancer Center, Smilow Cancer Hospital, discusses the design and key objectives of an ongoing phase 1a/b study (NCT05374538) of VIC-1911 as a monotherapy and in combination with sotorasib (Lumakras) in KRAS G12C–mutant non–small cell lung cancer (NSCLC).

VIC-1911 is a selective, reversible, orally active small molecular inhibitor of aurora kinase A (AUKRA) that is less myelosuppressive than dual AURKA and AURKB inhibition. Several preclinical studies have demonstrated the agent's activity as a monotherapy, and synergy with sotorasib, in KRAS G12C–mutant NSCLC cell lines with intrinsic and acquired sotorasib resistance, Goldberg begins.

The nonrandomized, open-label study aims to determine the safety, maximum-tolerated dose, dose-limiting toxicities, and recommended phase 2 dose of single-agent VIC-1911 and VIC-1911 plus sotorasib. Patients with advanced KRAS G12C–mutant NSCLC who have intrinsic or acquired sotorasib resistance, or are naïve to sotorasib, will be eligible for the study, Goldberg reports. Notably, patients are allowed to have received prior standard chemoimmunotherapy or immunotherapy alone.

A total of 140 patients will be enrolled on the study. In the dose-escalation portion of the study patients who have received prior G12C inhibition will be enrolled to either the monotherapy (cohort 1a) or combination (cohort 1b) cohort according to dose level. Patients who are G12C inhibitor–naïve will be enrolled in cohort 1b only.

Patients in the dose-expansion phase who have received prior G12C inhibition will be enrolled to either the monotherapy cohort (cohort 2a) or combination (cohort 2b) cohort according to dose level. Patients who are G12C inhibitor–naïve will receive the combination in cohort 2c only.

Disclosures: Dr Goldberg reports serving as a consultant or in an advisory role for AstraZeneca/ MedImmune, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Genentech/Roche, Genzyme, Janssen, Merck, Mirati Therapeutics, Regeneron, Summit Therapeutics, Takeda; she received research funding from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Merck, Mirati Therapeutics, Pfizer, Spectrum Pharmaceuticals; she received honoraria from Amgen.