Diagnosis and Main Criteria for Inclusion and Exclusion:
Each patient must meet all the following criteria to be enrolled in this study:
• Is ≥18 years of age at the time of signature of the main study ICF.
• Has ECOG PS of 0 or 1.
• Has a tumor with loss of MTAP protein or bi-allelic deletion of the MTAP gene
assessed centrally at study-sponsored laboratory, or locally with Sponsor approval.
• Has the following disease characteristics:
• Arm A: a) metastatic PDAC (no more than 2 prior lines of therapy) or b) locally
advanced or metastatic NSCLC (no more than 3 prior lines of therapy). Must also
have nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or
61.
• Arm B: a) metastatic PDAC (no more than 2 prior lines of therapy) or b) locally
advanced or metastatic NSCLC (no more than 3 prior lines of therapy). Must also
have KRAS, NRAS, or HRAS G12D mutation.
• Arm C: Previously untreated locally advanced or metastatic PDAC.
• Arm D: Locally advanced or metastatic PDAC (no more than 1 prior line of
therapy).
• Has adequate organ function.
• Has measurable disease based on RECIST v1.1.
• Has archival FFPE tumor specimen available with sufficient tumor tissue for central
retrospective IHC and NGS testing. If an archival FFPE tumor specimen is not
available, a newly obtained (before study treatment) tumor biopsy must be submitted
providing it is deemed medically safe and feasible or non significant risk to the
patient.
• Has not received prior treatment with a PRMT5 inhibitor or MAT2A inhibitor.
• Has not received prior treatment with RAS-targeted therapy, if assigned to Arms A
and B.
• Must not have enrolled in any Phase 3 clinical trial of RMC-6236 or RMC-9805 ,
even if randomized to standard of care control arm.