Dr Arbour on the Role of Zoldonrasib in KRAS G12D–Mutant NSCLC

“Zoldonrasib was well tolerated across all dose levels, including in the subset of patients who were treated at the candidate recommended phase 2 dose of 1200 mg once daily.”

Kathryn C. Arbour, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, detailed the safety profile and preliminary efficacy of zoldonrasib (RMC-9805) for the treatment of patients with KRAS G12D–mutated non–small cell lung cancer (NSCLC).

Within the safety population (n = 90), zoldonrasib was well tolerated across all dose levels, which included those treated with the recommended phase 2 dose of 1200 mg once daily, Arbour began. She noted that common treatment-related adverse effects (TRAEs) that occurred in at least 10% of patients comprised nausea (grade 1, 33%; grade 2, 6%; grade 3, 0%), diarrhea (20%; 3%; 1%), vomiting (13%; 4%; 0%), and rash (12%; 0%; 0%). Findings from the study also revealed that TRAEs were mostly grade 1 (54%), grade 2 (18%), or grade 3 (2%). TRAEs of interest regarding RAS inhibitors are commonly transaminitis and mucositis; however, these were considered rare within this patient population, she emphasized.

Notably, there were no grade 4/5 TRAEs or serious AEs observed. Additionally, any grade TRAES led to dose reduction in 4% of patients, dose interruptions in 9%, and and treatment discontinuations in 1%.

Of the 28 patients with NSCLC treated with the 1200-mg dose of zoldonrasib, 18 were treated at least 8 weeks before the data cutoff of December 2, 2024, Arbour explained. At the data cutoff, the objective response rate (ORR) was 61% per RECIST 1.1 criteria in the group, and the disease control rate (DCR) was 89%, which included complete responses, partial responses, and stable disease. Notably, the median time to response was 1.4 months (range, 1.2-2.8), and the median time on treatment was 2.6 months (range, 1.3-8.0).

The depth of response and disease control observed in the study highlight the potential role for zoldonrasib in this patient population, Arbour concluded.