Recruiting NCT07020221
A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors
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, Carboplatin + Pemetrexed + Pembrolizumab, Gemcitabine.
- Who it may be relevant to
- Registry conditions: Pancreatic Ductal Adenocarcinoma, Non Small Cell Lung Cancer, Colorectal Cancer, Solid Tumor, Adult. 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 1/2, Open-label Study of VS-7375, a KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and in Combination, in Patients With Advanced KRAS G12D-Mutated Solid Tumors
Overview
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.
Interventions
- Drug VS-7375
VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor. - Drug Cetuximab
Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR). - Drug Carboplatin + Pemetrexed + Pembrolizumab
A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer. - Drug Gemcitabine
A chemotherapy used for the treatment of several types of cancer including advanced or metastatic pancreatic ductal adenocarcinoma. - Drug Gemcitabine + Nab-paclitaxel
A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma.
Primary outcome measures
- Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 [Time frame: Up to 2.5 years]
- Part A: To identify the MTD or MFD [Time frame: Cycle 1 (each cycle is 21 days)]
- Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen [Time frame: Up to 2.5 years]
- Part C: To characterize the safety, tolerability, and AE profile of VS-7375 in combination regimens. [Time frame: From enrollment to the end of treatment; an average of 9 months]
- Part C: To identify a recommended dose for subsequent studies of combination dosed VS-7375. [Time frame: Cycle 1 (each cycle is 21 or 28 days)]
- Part D: To determine the preliminary anticancer activity of the optimal regimen of VS-7375 as identified in Part C [Time frame: Up to 2.5 years]
Secondary outcome measures (5)
- Part A: To characterize the PK of VS-7375 as 2L+ monotherapy administered on a daily oral schedule [Time frame: Up to 2.5 years]
- Part A: To evaluate the preliminary anticancer activity of VS-73753 as 2L+ monotherapy [Time frame: Up to 2.5 years]
- Parts B and D: To characterize the safety, tolerability, and AE profile of the recommended VS-7375 regimens from Part A and Part C [Time frame: Up to 2.5 years]
- Parts B, C, and D: To continue to evaluate the PK of VS-7375 as monotherapy and in combination with other systemic therapies [Time frame: Up to 2.5 years]
- Part C: Cohort C3: To evaluate the impact of VS-7375 on nab-paclitaxel PK [Time frame: Up to 2.5 years]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 13 centers
- Cedars-Sinai Medical Center — Los Angeles
- Johns Hopkins University — Baltimore
- Massachusetts General Hospital — Boston
- University of Michigan — Ann Arbor
- Washington University School of Medicine — St Louis
- Laura & Isaac Perlmutter Cancer Center at NYU Langone — New York
- Univ of Pennsylvania, Abramson Cancer Center — Philadelphia
- SCRI Oncology Partners — Nashville
- … and 5 more centers
Australia · 1 center
- Peninsula and Southeast Oncology — Frankston
Identifiers
NCT: NCT07020221 · VS-7375-101