Recruiting NCT07659795
A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Colorectal Cancer
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: VS-7375, cetuximab, panitumumab, Cetuximab + mFOLFOX6.
- Who it may be relevant to
- Registry conditions: Colorectal Cancer. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Phase 2, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, With and Without an Anti-EGFR Antibody, and With an Anti-EGFR Antibody and Chemotherapy, in Patients With Metastatic KRAS G12D-Mutated Colorectal Adenocarcinoma (TARGET-D 203)
Overview
This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab or panitumumab and cetuximab plus mFOLFOX in patients with metastatic KRAS G12D - mutated Colorectal Cancer
Interventions
- Drug VS-7375
Taken by mouth - Drug cetuximab
Intravenous infusion - Drug panitumumab
Intravenous infusion - Drug Cetuximab + mFOLFOX6
Intravenous infusion
Primary outcome measures
- Confirmed ORR by blinded independent central review (BICR) per RESIST v1.1 - 2L CRC only [Time frame: 6 months]
- To characterize the safety and tolerability of VS-7375 monotherapy or in combination with cetuximab or panitumumab, administered on a daily oral schedule in participants with KRAS G12D-mutated 2L+ CRC [Time frame: 6 months]
- To characterize the safety and tolerability of VS-7375 in combination with cetuximab + mFOLFOX, administered on a daily oral schedule in participants with KRAS G12D-mutated 1L CRC [Time frame: 6 months]
Secondary outcome measures (6)
- Confirmed ORR per RECIST v1.1 assessed by BICR (primary) and Investigator (secondary) assessments [Time frame: 24 months]
- Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, Cmax [Time frame: 20 weeks]
- Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, AUC [Time frame: 20 weeks]
- To evaluate Pharmacodynamics (PD) and other relevant blood tumor markers specific to tumor type [Time frame: Up to 2.5 years]
- To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30) [Time frame: 24 months]
- Time to next therapy [Time frame: 24 months]
Eligibility criteria
Inclusion criteria
- Histopathology confirmed metastatic CRC
- Measurable disease per RECIST 1.1
- Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing)
- ECOG PS=0 or 1
2L+ patients:
- Must have received at least 1 standard chemotherapy for metastatic colorectal adenocarcinoma
- Have documented disease progression during or following their most recent prior line of therapy
- Have either stable disease, partial response (PR), or complete response (CR) by RECIST v1.1 as the best overall response (BOR) during at least 1 prior systemic therapy.
1L patients:
- Treatment-naïve or received no more than 1 cycle of standard systemic therapy 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
- Receipt of prior direct RAS inhibitor
- Receipt of more than 1 investigational therapy
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Crossover
- Masking
- Single blind
- Primary purpose
- Treatment
Study locations
United States · 8 centers
- START Los Angeles — Los Angeles
- Valkyrie Clinical Trials — Los Angeles
- Moffitt Cancer Center — Tampa
- START Midwest — Grand Rapids
- START New Jersey — East Brunswick
- START Dallas Fort Worth — Fort Worth
- START Mountain Region — West Valley City
- UVA Comprehensive Cancer Center — Charlottesville
Australia · 2 centers
- Icon Cancer Centre South Brisbane — South Brisbane
- Icon Cancer Centre Adelaide — Kurralta Park
Identifiers
NCT: NCT07659795 · VS-7375-203 · 2026-526473-42-00