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RecruitingInterventionalPhase 2

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)

NCT ID: NCT07644559Sponsor: Verastem, Inc.Last updated: 2026-06-16

Summary

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

Arms & interventions

  • DrugVS-7375

    Taken by mouth

  • Drugcetuximab

    Subcutaneous infusion

Outcome measures

Primary

  • Confirmed ORR by blinded independent central review (BICR) per RESIST v1.1

    Overall Response Rate per RECIST version 1.1, per blinded independent central review (BICR)

    Time frame: 6 months

  • To characterize the safety and tolerability of VS-7375 monotherapy or in combination with cetuximab, administered on a daily oral schedule in participants with KRAS G12D-mutated PDAC.

    Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations.

    Time frame: 6 months

Secondary

  • 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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (8)

START- Los Angeles

Los Angeles, California, 90025

Recruiting
Hope Team · Contact
Navid Hafez, MD · Principal Investigator

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting
Brianna Holder · Contact
Dae-Won Kim, MD · Principal Investigator

START Midwest

Grand Rapids, Michigan, 49546

Recruiting
Hope Team · Contact
Sreenivasa Chandana, MD · Principal Investigator

Washington University

St Louis, Missouri, 63110

Recruiting
Olive Pressey · Contact
Kian-Huat Lim, MD · Principal Investigator

START New Jersey

East Brunswick, New Jersey, 08816

Recruiting
Hope Team · Contact
Bruno Fang, MD · Principal Investigator

START Dallas

Fort Worth, Texas, 76104

Recruiting
Hope Team · Contact
Salwan Almutar, MD · Principal Investigator

START- San Antonio

San Antonio, Texas, 78229

Recruiting
Hope Team · Contact
Drew Rasco, MD · Principal Investigator

START- Mountain Region

West Valley City, Utah, 84119

Recruiting
Julianna Daley · Contact
William McKean, MD · Principal Investigator