A Phase 1/2a Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors
Purpose
This study will assess the safety and efficacy of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation.
Conditions
- Pancreatic Ductal Adenocarcinoma
- Non Small Cell Lung Cancer
- Colorectal Cancer
- Solid Tumor, Adult
- G12D Mutated KRAS
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Individuals ≥18 years of age. - Agreement to sign and date an informed consent form (ICF) approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). - Histologic or cytologic evidence of locally advanced unresectable or metastatic solid tumor harboring a KRAS G12D mutation. - Must have received ≥1 prior line of standard systemic therapy for advanced or metastatic disease or experienced cancer progression within 6 months of neoadjuvant or adjuvant therapy. - Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate organ function - Adequate cardiac function - Recovered from all AEs due to previous therapies to Grade ≤1 or baseline. - Agreement to use highly effective contraception
Exclusion Criteria
- Underwent major surgical procedure as defined by the Investigator, other than for diagnosis, within 4 weeks prior to Cycle 1 Day 1, - Receipt of chemotherapy, targeted therapy, or radiotherapy (excluding palliative radiation) within 4 weeks or 5 half-lives, whichever is shorter, or immunotherapy within 4 weeks prior to Cycle 1 Day 1 - Treatment with any investigational drug at least 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1. - History of treatment with direct and specific KRAS G12D inhibitors. - Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases. - Inability to swallow oral medications. - Evidence or history of uncontrolled, clinically significant hematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation, neurologic, dermatologic, autoimmune, or allergic disease - Individuals who are pregnant or breastfeeding.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental VS-7375 Dose Escalation |
To determine the recommended phase 2 dose (RP2D) for VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation. |
|
Experimental Cetuximab + VS-7375 Dose Escalation |
To determine the recommended phase 2 dose (RP2D) for cetuximab + VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation. |
|
Experimental VS-7375 Recommended Phase 2 Dose Expansion |
To determine the efficacy of VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced PDAC and NSCLC harboring a KRAS G12D mutation. |
|
Experimental Cetuximab + VS-7375 Recommended Phase 2 Dose Expansion |
To determine the efficacy of cetuximab +VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced CRC harboring a KRAS G12D mutation. |
|
Recruiting Locations
Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Verastem, Inc.