RMC-9805

P1, N=290, Recruiting, Revolution Medicines, Inc.

TCR sequencing of T cells from tumors and blood harvested from treated mice revealed a significant increase in T cell diversity, as well as an increase in the number of shared TCR clones among all KRASG12D(ON) inhibitor-treated samples, suggesting cancer-associated antigen recognition.Overall, in these preclinical experiments, RMC-9805 exhibited direct anti-tumor effects and indirectly transformed the TME through inhibition of cancer cell-intrinsic KRASG12D oncogenic signaling. The increased antigen presentation, recognition, and T cell infiltration induced by inhibition of mutant KRAS may permit a more favorable environment for immune-directed ‘companion’ therapies, such as checkpoint inhibitors, cellular therapies, and/or vaccines.[1] Timar, J. et al, 2020 [2] Hamarsheh, S. et al, 2020 [3] Sumimoto, H. et al, 2016

Furthermore, RMC-9805 combination therapies drove regressions in CRC models relatively less responsive to monotherapy. Supported by these findings, RMC-9805 is currently in IND-enabling development to permit clinical evaluation of single agent and combination strategies in patients with KRASG12D tumors.