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

Inclusion Criteria:

• Histopathology confirmed unresectable locally advanced or metastatic NSCLC
• 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
• Received prior treatment with a platinum-based chemotherapy regimen and an immune checkpoint inhibitor in the advanced, non-resectable setting.
• Have documented disease progression during or following their most recent prior line of therapy.

Patients with 2L/3L on stable or preferred dose:

• Received at least 1 and no more than 2 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC.

Patients with 2L-4L with brain metastases:

• Received at least 1 and no more than 3 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC.
• Have asymptomatic and untreated brain metastases
• At least 1 untreated measurable brain lesion per mRECIST v1.1 with a long axis ≥ 0.5 cm and ≤ 3 cm.

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
• 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