ES30.05 Combination Therapy Approaches to Target Rare Mutations (ErbB Receptors and KRAS pG12C) in NSCLC

Abstract

Several rare driver mutations have been investigated in NSCLC, with some successes and some failures. With better understanding of the biology of various subtypes of each rare mutation will help not only to choose the right inhibitor for the right patient population, but also to elucidate the respective resistance mechanisms and their therapeutic strategies. However, a significant gap still exists when applying pre-clinical results to clinical outcome and activation of bypass pathways represents an important resistance mechanism to driver mutation inhibitors. More recently, experimental combination therapy approach targeting rare mutations in NSCLC has emerged as an optional promising strategy to overcome this issue. Several experiments have been carried out to evaluate the synergism of combination therapy approach both in vitro and in vivo. Additionally, several early phase 1 clinical trials have been carried out to investigate the feasibility of treatment with combination therapy approach with emerging both bi-specific antibodies (BSAs) and immunotherapies. It is still not clear whether monotherapy of highly potent selective inhibitors targeting rare mutation or combination approach strategy have superior antitumor activity. Further preclinical and clinical evaluation of concurrent inhibition of the bypass pathways and driver rare mutation is warranted. This session review will introduce and analyze the rationalities and clinical investigation associated with various combination strategies targeting rare mutations (ErbB Receptors and KRAS pG12C) in NSCLC.