Site Editor
Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Friday, June 6, 2025
A phase I clinical trial presented at the 2025 AACR Annual Meeting found that divarasib plus migoprotafib for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC) demonstrated preliminary clinical activity. Jia Luo, MD, of the Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues found that the combination had an acceptable safety profile as well.
The ongoing study (NCT04449874) has, as of April 2024, treated 74 patients with NSCLC with either 200 mg or 400 mg of divarasib daily, in combination with 20, 40, or 60 mg of oral migoprotafib. Treatment continued until intolerable toxicity or disease progression, and circulating tumor DNA (ctDNA) analyses were performed at cycle 1 day 1 and cycle 3 day 1. Among the 74 patients, the lines of prior systemic therapy ranged between 0 and 7, with a median of 2. Forty-eight patients had no prior KRAS G12Ci exposure, and all of these 48 patients had measurable disease at baseline.
Among the patients who had no prior KRAS G12Ci exposure, the overall response rate was 43.8%, with a median progression-free survival of 15.2 months (CI [confidence interval] 95% 8.4-not estimated). During ctDNA analysis at cycle 3 day 1, a decline in ctDNA level was observed upon divarasib plus migoprotafib treatment similar to that of divarasib alone. Seventy of the 74 patients experienced at least one treatment-related adverse event, the most common being diarrhea, nausea, vomiting, peripheral edema, increased blood creatine phosphokinase, fatigue, increased amylase, increased aspartate aminotransferase, and increased alanine aminotransferase. This lead to divarasib discontinuation in 2 patients, and migoprotafib discontinuation in 5. Thirty-two patients experienced grade 3-4 treatment-related adverse events, and none experienced grade 5.
While the safety profile was acceptable in phase I of this trial, the study authors stated that updated data will be presented in the future. Future presentations will also continue to look at patients both with and without prior KRAS G12Ci exposure.
Disclosures: The study authors reported no conflicts of interest.
JNCCN Spotlights
Resources
For your Patients
