Sean Callaghan

Sean Callaghan asked about the staggering of enrollment for RASolute 302, 305, 309, and 303 protocol components to ensure a representative sample of mutations and avoid enrichment of non-G12D patients. He also inquired about expectations for G12D versus G12V and G12R patient performance in the G12P arm of RASolute 303, given G12D's perceived aggressiveness.

Answer

Chief Medical Officer Wei Lin explained that enrollment is managed through global site selection, ensuring fair representation across all-comer (RASolute 303) and G12D mutant (RASolute 305, 309) populations. He noted that control arms vary, and local practices influence site selection, with a large patient pool ensuring sufficient enrollment. Chairman and CEO Mark A. Goldsmith added that differences in patient performance among G12D, G12V, and G12R mutations are not well-established and often conflicting. He emphasized that randomization ensures balance between control and experimental arms in any given trial, mitigating inherent bias.

Sean Callaghan inquired about the staggering of enrollment for RASolute 302, 305, and 309, and the 303 protocol components to ensure a representative sample of mutations in 303 and avoid enrichment of non-G12D patients. He also asked about expectations for G12D versus G12V and G12R patient performance in the G12P arm of 303, given G12D's perceived aggressiveness.

Answer

Wei Lin, Chief Medical Officer, explained that site selection and global trial design would manage patient representation, ensuring fair distribution across trials. She noted the commonality of PDAC patients and the variety of sites available. Mark Goldsmith, Chairman and CEO, added that 85% of PDAC cases have a G12 mutation, making dramatic bias unlikely, and randomization ensures balance between control and treatment groups. He also stated that well-established differences in patient performance among specific RAS mutations are not consistently observed.