A Phase 2, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and with Cetuximab, in Patients with Metastatic KRAS G12D-Mutated Pancreatic Cancer (TARGET-D 201)

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