This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab in patients with metastatic KRAS G12D - mutated Pancreatic Cancer

Inclusion Criteria:

• Histopathology confirmed PDAC
• Measurable disease per RECIST 1.1
• Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing)
• ECOG PS=0 or 1

Adequate organ function

VS-7375 + cetuximab (2L PDAC) :

-Received only 1 prior Tx in the metastatic setting; prior adjuvant counts as a line if progressed within 6 months

VS-7375 + cetuximab (1L PDAC) :

-Treatment-naïve or received ≤ 1 cycle of SoC for metastatic disease

Exclusion criteria:

• Have any other documented co-existing common RAS mutation(s)
• Prior anti-cancer Tx within 4 weeks or drug-specific timeline within first treatment dose, whichever shorter
• Major surgery within 4 weeks of first treatment dose
• Radiation therapy (RT) within 1 week of first treatment dose; RT to brain or lung within 2 weeks of first treatment dose
• History of drug-induced Interstitial Lung Disease
• Receipt of prior direct RAS inhibitor
• Untreated or symptomatic CNS metastasis
• Receipt of strong CYP3A4 inhibitor/inducer or CYP3A4 sensitive substrates with narrow therapeutic index within 14 days or drug-specific timeline within first treatment dose, whichever is shorter
• Receipt of PPI or H2 blocker within 5 days
• Inability to swallow oral medication
• Other protocol-defined inclusion/exclusion criteria may apply