In today’s episode, supported by Revolution Medicines, we spoke with Kathryn C. Arbour, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, about 2 important abstracts presented at the 2024 AACR Annual Meeting that explore novel RAS-targeted approaches in non–small cell lung cancer (NSCLC).

Our discussion focused on early clinical findings with zoldonrasib (RMC-9805) and daraxonrasib (RMC-6236), both of which are RAS(ON) inhibitors under investigation for the treatment of patients with RAS-mutant NSCLC. Zoldonrasib, a KRAS G12D-selective tri-complex inhibitor, was evaluated in a phase 1 trial (NCT06040541) in patients with previously treated, advanced KRAS G12D–mutated solid tumors, including NSCLC. Daraxonrasib, a multi-selective RAS(ON) inhibitor, was highlighted in another phase 1 trial (NCT05379985) in patients with advanced RAS-mutant tumors, including previously treated NSCLC; notably, this AACR presentation focused on the association between early on-treatment circulating tumor DNA level reduction and clinical response with the agent.

In this episode, Dr Arbour shared insights into the mechanisms of action behind these therapies, their respective clinical trial designs, and the potential implications that early data with the agents may have for the evolving RAS-mutant NSCLC treatment paradigm.