A Phase 1/2 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. - 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, NSCLC, or solid tumors 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. |
|
|
Experimental VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Escalation |
To determine the recommended phase 2 dose (RP2D) for VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab in patients with advanced 1L NSCLC harboring a KRAS G12D mutation. |
|
|
Experimental VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Expansion |
To determine the efficacy of VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab at the RP2D in patients with advanced 1L NSCLC harboring a KRAS G12D mutation. |
|
|
Experimental VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Escalation |
To determine the recommended phase 2 dose (RP2D) for VS-7375 in combination with gemcitabine/nab-paclitaxel in patients with advanced PDAC harboring a KRAS G12D mutation. |
|
|
Experimental VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Expansion |
To determine the efficacy of VS-7375 in combination with gemcitabine/nab-paclitaxel at the RP2D in patients with advanced PDAC harboring a KRAS G12D mutation. |
|
|
Experimental VS-7375 + Gemcitabine Dose Escalation |
To determine the RP2D for VS-7375 in combination with gemcitabine in patients 75 years or older with advanced PDAC harboring a KRAS G12D mutation. |
|
|
Experimental VS-7375 + Gemcitabine Dose Expansion |
The determine the efficacy of VS-7375 in combination with gemcitabine at the RP2D in patients 75 years or older with advanced PDAC harboring a KRAS G12D mutation. |
|
Recruiting Locations
Cedars-Sinai Medical Center
Los Angeles, California 90048
Los Angeles, California 90048
Johns Hopkins University
Baltimore, Maryland 21287
Baltimore, Maryland 21287
Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
University of Michigan
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
Washington University School of Medicine
St Louis, Missouri 63110
St Louis, Missouri 63110
Laura & Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
New York, New York 10016
Univ of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
SCRI Oncology Partners
Nashville, Tennessee 37203
Nashville, Tennessee 37203
MD Anderson Cancer Center
Houston, Texas 77030
Houston, Texas 77030
Huntsman Cancer Institute
Salt Lake City, Utah 84112
Salt Lake City, Utah 84112
University of Virginia
Charlottesville, Virginia 22908
Charlottesville, Virginia 22908
Virginia Cancer Specialists
Fairfax, Virginia 22031
Fairfax, Virginia 22031
Virginia Mason Medical Center
Seattle, Washington 98101
Seattle, Washington 98101
More Details
- Status
- Recruiting
- Sponsor
- Verastem, Inc.