Minal Barve

Abstract Daraxonrasib is an orally bioavailable RAS(ON) multi-selective tri-complex inhibitor of the oncogenic mutant and wild-type variants of N, H and KRAS. We previously reported encouraging efficacy in a phase 1/2 clinical trial evaluating daraxonrasib monotherapy at clinically active dose levels in patients with previously treated, RAS mutant metastatic pancreatic adenocarcinoma (PDAC), providing the basis for confirmatory evaluation in the randomized phase 3 RASolute 302 clinical trial.

NKG2A is an immune inhibitory receptor expressed on natural killer cells and T cells. Cancer cells exploit the NKG2A inhibitory pathway, thereby protecting themselves against antitumor immunity. NKG2A targeting may contribute to anti-programmed cell death protein 1 immune checkpoint activity. Our first-in-human, phase 1 study of an anti-NKG2A antibody demonstrated a favorable safety profile and preliminary antitumor activity in unselected, heavily pretreated patients with advanced malignancies.

Abstract SHR-A1811, an antibody‒drug conjugate consisting of the anti-HER2 antibody trastuzumab conjugated via a cleavable linker to a topoisomerase I inhibitor payload, demonstrated substantial antitumor activity in patients with heavily treated HER2-expressing or mutated advanced solid tumors. The main analysis was reported, and this is a long-term follow-up of the HORIZON-X trial (NCT04446260).