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
New KRAS G12D Cancer Drug VS-7375 Trial Recruiting
Plain English Summary
A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors is a Phase 2 clinical trial sponsored by Verastem, Inc. studying Pancreatic Ductal Adenocarcinoma, Non Small Cell Lung Cancer, Colorectal Cancer, Solid Tumor, Adult, G12D Mutated KRAS. This trial tests a new drug called VS-7375, alone and with other treatments, for advanced cancers with a specific KRAS G12D mutation. It is for adults with certain advanced solid tumors, including pancreatic, lung, and colorectal cancers, that have this specific genetic change. Participation involves taking the study drug(s) and regular medical check-ups, including tests to monitor your health and the cancer's response. Alternative treatments may include standard chemotherapy, targeted therapies, or immunotherapy, depending on the cancer type and prior treatments. The trial aims to enroll 295 participants.
Official Summary
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.
Who Can Participate
Here is what you need to know about eligibility for this trial. Adults aged 18 and older with advanced solid tumors confirmed to have a KRAS G12D mutation. Patients must have cancer that can be measured by scans and be in good enough general health to participate. Individuals with active brain metastases or those who have recently had major surgery or other cancer treatments may not be eligible. Pregnant or breastfeeding individuals cannot join this study. This trial is studying Pancreatic Ductal Adenocarcinoma, Non Small Cell Lung Cancer, Colorectal Cancer, Solid Tumor, Adult, G12D Mutated KRAS, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.
What They're Measuring
The primary outcomes will show how safe VS-7375 is, what side effects may occur, and whether the drug helps shrink tumors or control cancer growth. The specific primary outcome measures are: Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 (Up to 2.5 years); Part A: To identify the MTD or MFD (Cycle 1 (each cycle is 21 days)); Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen (Up to 2.5 years); Part C: To characterize the safety, tolerability, and AE profile of VS-7375 in combination regimens. (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. (Cycle 1 (each cycle is 21 or 28 days)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.
Why This Trial Matters
This trial addresses a critical need for new treatments for KRAS G12D-mutated cancers, a common and difficult-to-treat genetic alteration in many solid tumors. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Pancreatic Ductal Adenocarcinoma, Non Small Cell Lung Cancer, Colorectal Cancer, Solid Tumor, Adult, G12D Mutated KRAS, where improved treatment options are needed.
Investor Insight
This trial targets a significant unmet need in KRAS-mutated cancers, a large market with limited effective therapies, suggesting potential for a valuable new treatment if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.
Is This Trial Right for Me?
Ask your doctor about the specific risks and benefits of VS-7375 and how it compares to your other treatment options. Be prepared for regular clinic visits for drug administration, blood tests, scans, and physical exams to monitor your health and cancer. You will need to use effective birth control during the study and for a period afterward if you are able to become pregnant or can cause pregnancy. This trial is currently recruiting participants. The trial is being conducted at 13 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: NON_RANDOMIZED
- Model: SEQUENTIAL
- Masking: NONE
- Enrollment: 295 participants
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 Outcomes
- Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 (Up to 2.5 years)
- Part A: To identify the MTD or MFD (Cycle 1 (each cycle is 21 days))
- Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen (Up to 2.5 years)
- Part C: To characterize the safety, tolerability, and AE profile of VS-7375 in combination regimens. (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. (Cycle 1 (each cycle is 21 or 28 days))
Secondary Outcomes
- Part A: To characterize the PK of VS-7375 as 2L+ monotherapy administered on a daily oral schedule (Up to 2.5 years)
- Part A: To evaluate the preliminary anticancer activity of VS-73753 as 2L+ monotherapy (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 (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 (Up to 2.5 years)
- Part C: Cohort C3: To evaluate the impact of VS-7375 on nab-paclitaxel PK (Up to 2.5 years)
Full Eligibility Criteria
Key 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 Key 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.
Trial Locations
- Cedars-Sinai Medical Center, Los Angeles, California, United States
- Johns Hopkins University, Baltimore, Maryland, United States
- Massachusetts General Hospital, Boston, Massachusetts, United States
- University of Michigan, Ann Arbor, Michigan, United States
- Washington University School of Medicine, St Louis, Missouri, United States
- Laura & Isaac Perlmutter Cancer Center at NYU Langone, New York, New York, United States
- Univ of Pennsylvania, Abramson Cancer Center, Philadelphia, Pennsylvania, United States
- SCRI Oncology Partners, Nashville, Tennessee, United States
- MD Anderson Cancer Center, Houston, Texas, United States
- Huntsman Cancer Institute, Salt Lake City, Utah, United States
- ...and 3 more locations
Frequently Asked Questions
What is clinical trial NCT07020221?
NCT07020221 is a Phase 2 INTERVENTIONAL study titled "A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors." It is currently recruiting and is sponsored by Verastem, Inc.. The trial targets enrollment of 295 participants.
What conditions does NCT07020221 study?
This trial investigates treatments for Pancreatic Ductal Adenocarcinoma, Non Small Cell Lung Cancer, Colorectal Cancer, Solid Tumor, Adult, G12D Mutated KRAS. The primary condition under study is Pancreatic Ductal Adenocarcinoma.
What treatments are being tested in NCT07020221?
The interventions being studied include: VS-7375 (DRUG), Cetuximab (DRUG), Carboplatin + Pemetrexed + Pembrolizumab (DRUG), Gemcitabine (DRUG), Gemcitabine + Nab-paclitaxel (DRUG). VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor.
What does Phase 2 mean for NCT07020221?
Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.
What is the current status of NCT07020221?
This trial is currently "Recruiting." It started on 2025-06-24. The estimated completion date is 2028-12.
Who is sponsoring NCT07020221?
NCT07020221 is sponsored by Verastem, Inc.. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT07020221?
The trial aims to enroll 295 participants. The trial is currently recruiting and accepting new participants.
How is NCT07020221 designed?
This is a interventional study, uses non_randomized allocation, follows a sequential design, employs none masking.
What are the primary outcomes being measured in NCT07020221?
The primary outcome measures are: Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 (Up to 2.5 years); Part A: To identify the MTD or MFD (Cycle 1 (each cycle is 21 days)); Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen (Up to 2.5 years); Part C: To characterize the safety, tolerability, and AE profile of VS-7375 in combination regimens. (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. (Cycle 1 (each cycle is 21 or 28 days)). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT07020221 being conducted?
This trial is being conducted at 13 sites, including Los Angeles, California; Baltimore, Maryland; Boston, Massachusetts; Ann Arbor, Michigan and 9 more sites (United States, Australia).
Where can I find official information about NCT07020221?
The official record for NCT07020221 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT07020221. This government database provides the most up-to-date and detailed information about the trial.
What is NCT07020221 testing in simple terms?
This trial tests a new drug called VS-7375, alone and with other treatments, for advanced cancers with a specific KRAS G12D mutation. It is for adults with certain advanced solid tumors, including pancreatic, lung, and colorectal cancers, that have this specific genetic change.
Why is this trial significant?
This trial addresses a critical need for new treatments for KRAS G12D-mutated cancers, a common and difficult-to-treat genetic alteration in many solid tumors.
What are the potential risks of participating in NCT07020221?
Common side effects may include fatigue, nausea, diarrhea, and changes in blood counts. More serious side effects can occur, including liver problems, lung inflammation, or heart issues, which will be closely monitored. The study drug may interact with other medications, so it's important to tell your doctor about all medicines you are taking. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT07020221?
Ask your doctor about the specific risks and benefits of VS-7375 and how it compares to your other treatment options. Be prepared for regular clinic visits for drug administration, blood tests, scans, and physical exams to monitor your health and cancer. You will need to use effective birth control during the study and for a period afterward if you are able to become pregnant or can cause pregnancy. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT07020221 signal from an investment perspective?
This trial targets a significant unmet need in KRAS-mutated cancers, a large market with limited effective therapies, suggesting potential for a valuable new treatment if successful. This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.
What happens if the treatment in this trial doesn't work?
Participation involves taking the study drug(s) and regular medical check-ups, including tests to monitor your health and the cancer's response. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.