Abstract CT042: Impact of food on the pharmacokinetics of olomorasib in healthy participants

Abstract Introduction: Olomorasib is a potent, orally bioavailable, and highly selective second-generation inhibitor of KRAS G12C, currently under evaluation in 1L NSCLC in the Phase 3 study SUNRAY-01 (NCT06119581). Food can alter the rate and/or extent of absorption of orally administered agents, which may have potential clinical implications in the treatment of patients. The effect of food on olomorasib pharmacokinetics (PK) was assessed in healthy adults. Methods: This was a Phase 1, open-label, randomized, 2-period, 2-sequence, crossover study to evaluate the impact of a high-fat or low-fat meal on PK after a single oral dose of 100 mg olomorasib in healthy participants (NCT05824858). Forty-eight participants aged 19 to 47 years were enrolled in one of two cohorts (high-fat vs. fasted N=24; or low-fat vs. fasted N=24). Olomorasib plasma concentrations were measured up to 72 hours post-dose using a validated bioanalytical method. Non-compartmental analysis was used to calculate PK parameters, and a linear mixed-effects model was used for statistical inference. Safety and tolerability were also assessed. Results: High-fat meal intake delayed the absorption of olomorasib (median Tmax shift by 3 hours) associated with 28% reduction of olomorasib Cmax. However, this did not appreciably affect total systemic exposure (AUC0-inf); Geometric LS mean ratios (fed/fasted) [estimate (90% CI)] were 0.723 (0.565 - 0.925), and 1.130 (1.006 - 1.270) for Cmax and AUC0-inf, respectively. Low-fat meal intake resulted in approximately 30% and 25% reduction in olomorasib Cmax and AUC0-inf, respectively, but Tmax remained unchanged at approximately 3 hours; Geometric LS mean ratios (fed/fasted) [estimate (90% CI)] were 0.699 (0.554 - 0.884) and 0.745 (0.657 - 0.845) for Cmax and AUC0-inf, respectively. Olomorasib terminal half-life was similar across fed and fasted conditions at approximately 7 hours. A single oral dose of olomorasib was well tolerated when administered in the fasted or fed state. Treatment-emergent adverse events related to olomorasib were dizziness, headache, pruritus, and haematuria, each of which were mild, reversible, and reported in 1 participant. There were no SAEs or TEAEs leading to treatment discontinuation during the study. Conclusions: Food intake does not have a clinically relevant impact on the olomarasib PK as its Cmax and AUC(0-inf) with both meal conditions are within the inter-subject variability in exposure. Olomorasib can safely be taken with or without food, one of several patient-centered design features incorporated into the ongoing registrational SUNRAY-01 trial. Citation Format: Sophie Callies, Jessica Appert, Ashleigh Campillo, Vivian Rodriguez Cruz, Raimund Peter, Brian Sharkey, Carla Visseren - Grul, Yingying Guo-Avrutin. Impact of food on the pharmacokinetics of olomorasib in healthy participants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT042.