A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer
TARGET-D 202
A Phase 2, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Patients With Previously Treated, Advanced KRAS G12D-Mutated Non-Small Cell Lung Cancer (TARGET-D 202)
2 other identifiers
interventional
105
1 country
3
Brief 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 Non-Small Cell Lung Cancer
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 nonsmall-cell-lung-cancer
Started Jul 2026
Shorter than P25 for phase_2 nonsmall-cell-lung-cancer
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 15, 2026
CompletedFirst Posted
Study publicly available on registry
June 22, 2026
CompletedStudy Start
First participant enrolled
July 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
July 30, 2026
July 1, 2026
11 months
June 15, 2026
July 28, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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)
6 months
To characterize the safety and tolerability of VS-7375 monotherapy administered on a daily oral schedule in participants with KRAS G12D-mutated NSCLC
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations
6 months
Secondary Outcomes (6)
Confirmed ORR per RECIST v1.1 assessed by BICR (primary) and Investigator (secondary) assessments
24 months
Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, Cmax
20 weeks
Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, AUC
20 weeks
To evaluate Pharmacodynamics (PD) and other relevant blood tumor markers specific to tumor type
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)
24 months
- +1 more secondary outcomes
Other Outcomes (1)
Imaging of tumor metabolism changes
24 months
Study Arms (3)
VS-7375 Monotherapy 2L/3L
EXPERIMENTAL2L/3L VS-7375 dose
VS-7375 Monotherapy 2L/3L Preferred Dose
EXPERIMENTAL2L/3L Preferred VS-7375 dose
2L-4L with brain metastasis
EXPERIMENTAL2L-4L VS-7375 dose
Interventions
Taken by mouth
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Verastem, Inc.lead
Study Sites (3)
START LA
Los Angeles, California, 90025, United States
START New Jersey
East Brunswick, New Jersey, 08816, United States
START Fort Worth
Fort Worth, Texas, 76104, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 15, 2026
First Posted
June 22, 2026
Study Start
July 1, 2026
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
December 1, 2028
Last Updated
July 30, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share