A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer

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