A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer (TARGET-D 202)

Verastem

Status and phase: Not yet enrolling; Phase 2

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: VS-7375

Study type: Interventional

Funder types: Industry

Identifiers

NCT07659782

2026-526472-23-00 (EU Trial (CTIS) Number)

VS-7375-202

Details and patient eligibility

About

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

Enrollment: 105 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

---

105 participants in 3 patient groups

VS-7375 Monotherapy 2L/3L

Experimental group

Description:

2L/3L VS-7375 dose

Treatment:

Drug: VS-7375

VS-7375 Monotherapy 2L/3L Preferred Dose

Experimental group

Description:

2L/3L Preferred VS-7375 dose

Treatment:

Drug: VS-7375

2L-4L with brain metastasis

Experimental group

Description:

2L-4L VS-7375 dose

Treatment:

Drug: VS-7375