Pancreatic CancerPhase 1/2Panc 004NCT07824960
Neoadjuvant Avutometinib/Defactinib and mFOLFIRINOX Combination Therapy in Pancreatic Adenocarcinoma
A Phase 1/2 study testing Avutometinib (VS-6766) + Defactinib (VS-6063) in people with Pancreatic Cancer and PDAC - Pancreatic Ductal Adenocarcinoma, run by University of Virginia at 1 site in United States.
Trial summary
The goal of this study is to find out if taking two oral study drugs (avutometinib and defactinib) are safe for patients with pancreatic ductal adenocarcinoma (PDAC). Researchers also want to see if the drugs can slow down tumor growth and shrink tumors for possible surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, PDAC - Pancreatic Ductal Adenocarcinoma, Metastatic Pancreatic Carcinoma
- What is being tested?
- Avutometinib (VS-6766) + Defactinib (VS-6063)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to Apr 2030
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form.
- Individuals ≥ 18 years of age.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Ability to take oral medication and be willing to adhere to the study intervention regimen.
- Ability to receive mFOLFIRINOX.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
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- Adenocarcinoma of the pancreas, confirmed by histology or cytology.
- Part A: Metastatic pancreatic cancer
- Part B: Borderline resectable or locally advanced PDAC not eligible for primary surgical resection per institutional standards and following a multidisciplinary discussion at local tumor board
- No prior systemic or localized treatment for PDAC.
- Radiographically measurable disease of at least one site by computed tomography (CT) or magnetic resonance (MR) imaging, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Individuals must have adequate organ function defined by the following laboratory parameters:
- Absolute neutrophil count (ANC): ≥ 1500/mm3 Platelets: ≥100,000/mm3 Hemoglobin: ≥9 g/dL Serum Creatinine: ≤ 1.5 x ULN or creatinine clearance rate of ≥ 50 mL/min as calculated by the Cockcroft-Gault formula Bilirubin: ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 3x ULN is allowed).
- AST and ALT: ≤ 2.5 x ULN or ≤ 5 x ULN for patients with liver metastasis INR: ≤ 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the presence of anticoagulation Creatine phosphokinase (CPK): ≤ 2.5 x ULN
- Baseline corrected QT interval (QTc) interval ≤ 480 millisecond (ms) (CTCAE v5.0, Grade 0-1) using Fridericia's QT correction formula.
- Patients with a left bundle branch block (LBBB) > 480 ms will need their QTc calculated by Bazett (QTc = QT(measured) - 0.5 × QRS(LBBB)).
Who cannot join
- Patients with pancreatic neuroendocrine tumors (PNET), islet cell tumors, mucinous cystic, acinar or squamous (≥ 50%) histology are excluded.
- Prior treatment for pancreatic ductal adenocarcinoma.
- Presence of distant metastases (Part B only).
- Presence of symptomatic ascites or the need for paracentesis within 2 weeks prior to registration.
- Major surgery within 4 weeks (excluding placement of vascular access) of registration.
- Patients with a prior or concurrent malignancy within past 5 years whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Examples of malignancies that may be permitted include non-melanoma skin cancer, localized prostate cancer treated with curative intent or under active surveillance, localized thyroid cancer (papillary or follicular), non-muscle invasive low-grade bladder cancer, resected gastrointestinal stromal tumor, stage I testicular cancer post orchiectomy, WHO (World Health Organization) grade 1 meningioma.
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- Prior treatment with either inhibitors of the RAS/MAPK pathway [e.g., MEK inhibitors] or inhibitors of FAK within the last 6 months.
- Patients on treatment with warfarin within 5 days of registration. Patients on warfarin for deep vein thrombosis or pulmonary embolism can be converted to low-molecular-weight heparin or direct oral anticoagulants (DOACs).
- Participants requiring medications or supplements with potential for drug-drug interactions, specifically strong CYP3A4 or CYP2C9 inhibitors or inducers (Table 7). Participants must be off these medications for 7 days prior to the first dose of study intervention(s). These substances should also be avoided during the course of therapy.
- Patients with known UGT1A1 deficiency based on genetic analysis of the UGT1A1 gene.
- Receipt of live vaccines (not limited to the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG) within 30 days of registration. Seasonal influenza vaccines for injection are generally killed virus vaccines and are permitted. However, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not permitted.
- Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- Active Human Immunodeficiency Virus (HIV) infection, unless patient is on effective anti-retroviral therapy and was shown to have a negative viral load within 6 months of registration.
- Active Hepatitis B Virus (HBV) or Hepatitis C (HCV) infection, unless patient is on antiviral therapy and was shown to have a negative viral load test within 6 months of registration.
- Active skin disorder that requires current systemic therapy.
- Concurrent ocular disorders:
- Patients with history of glaucoma or history of retinal vein occlusion (RVO).
- Patients with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO.
- Patients with active or chronic, visually significant corneal disorders, other active ocular conditions requiring ongoing therapy that prevent adequate monitoring of drug-induced keratopathy. Examples of visually significant corneal disorders include corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions. Visually significant corneal disorders do NOT include dry eyes, blepharitis, and uncomplicated corneal erosions.
- Patients with history of interstitial lung disease (ILD) or pulmonary fibrosis.
- Patients with history of severe obstructive pulmonary disease on long-term, home oxygen.
- Patients with congestive heart failure III/ IV cardiac disease (New York Heart Association [NYHA]), myocardial infarction within the last 6 months, unstable arrhythmias or unstable angina.
- Patients receiving immunosuppressive or myelosuppressive medications that, in the opinion of the investigator, would increase the risk of serious neutropenic complications. Subjects receiving replacement therapy of ≤10 mg of prednisone (or the equivalent hydrocortisone dose) per day are eligible.
- History of prior allogeneic stem cell or solid organ transplantation.
- Patients with impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease.
- Patients with pre-existing peripheral neuropathy of CTCAE Grade ≥2 (severe symptoms limiting self-care ADL (activity of daily living)).
- Patients with a history of allergy or known hypersensitivity to any of the study treatments or any of their excipients as outlined in the respective package insert.
- Individuals with reproductive potential who do not agree to use highly effective method of contraceptive as described in Lifestyle Considerations (sections 5.4.2 and 5.4.3).
- Patients who are pregnant or breastfeeding.
- Treatment with another investigational drug during the study participation.
- Any other medical condition, related to the underlying disease (e.g., cardiac, gastrointestinal, pulmonary, psychiatric, neurological) that in the opinion of the investigator would place the patient at unacceptably high risk for toxicity.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Virginia Health System
Charlottesville, Virginia, 22908
Matthew Reilley, MD, mr7db@uvahealth.org
About this study
Official title: Neoadjuvant Avutometinib/Defactinib and mFOLFIRINOX Combination Therapy in Pancreatic Adenocarcinoma: A Phase IB/II Safety and Efficacy Study
The goal of this study is to find out if taking two oral study drugs (avutometinib and defactinib) are safe for patients with pancreatic ductal adenocarcinoma (PDAC). Researchers also want to see if the drugs can slow down tumor growth and shrink tumors for possible surgery. These drugs are approved by the FDA to treat a certain kind of ovarian cancer. This study has two parts:
- Part A is for patients whose cancer has spread to other parts of the body.
- Part B is for patients whose cancer has not spread, but who cannot have surgery.
Participants will take both drugs as told by their doctor with their regular cancer medicine. Participants will also give blood samples throughout the study. These samples will help researchers learn about how participants respond to treatment and about their pancreatic cancer.
Read the detailed description
Participants in part A will take the study drugs in 28-day cycles for up to 6 cycles with their chemotherapy. Participants whose cancer is not getting worse (known as disease control) may continue the study drugs in combination with maintenance chemotherapy until their disease worsens or negative side effects are noted.
Participants in part B will take the study drugs in 28-day cycles for up to 6 cycles with their chemotherapy. After cycle 4 and cycle 6, participants will have their disease re-assessed with consideration for surgery. Participants whose cancer is not getting worse (disease control) but are ineligible for surgery may continue the study drugs in combination with maintenance chemotherapy until their disease worsens or negative side effects are noted.
- Conditions
- Pancreatic Cancer, PDAC - Pancreatic Ductal Adenocarcinoma, Metastatic Pancreatic Carcinoma, Locally Advanced Pancreatic Cancer
- Being tested
- Avutometinib (VS-6766) + Defactinib (VS-6063)
- Keywords
- avutometinib, defactinib, PDAC, pancreatic cancer, dual RAF/MEK inhibitor, RAF inhibitor, MEK inhibitor
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avutometinib (VS-6766) + Defactinib (VS-6063)Drug
Participants will receive avutometinib and defactinib in combination with mFOLFIRINOX (standard of care chemotherapy) in 28-day cycles for up to 6 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant avutometinib + defactinib with standard of care chemotherapy | Experimental | Avutometinib and defactinib will be taken for 3 weeks, followed by a 1-week rest period in each 4 week cycle. Receives: Drug: Avutometinib (VS-6766) + Defactinib (VS-6063) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (DLTs) - Part A
For each participant, we will determine DLTs during first cycle of neoadjuvant therapy
Measured: 1 cycle (28 days)
Objective response (OR) - Part B
PR (partial response) or CR (complete response) per RECIST criteria
Measured: through 6 cycles (each cycle is 28 days)
Secondary outcomes (3)
TRAEs (Treatment-related adverse events)
Cumulative incidence of adverse events as defined by CTCAE v5 tabulating frequency, proportion, and severity
Measured: Up to 30 days after completion of study treatment (average of 6 months)
(Part B only): Surgical resection rate
We will determine the number of participants eligible for surgical resection out the total number of study participants.
Measured: after all participants complete up to 6 cycles (each cycle is 28 days)
EFS (event free-survival)
disease progression, disease recurrence after surgery, or death
Measured: through study completion (an average of a year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2026
- Study start1 Oct 2026 (estimated)
- Primary completionApr 2029 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Verastem, Inc.
- Responsible party
- Principal investigator, Matthew Reilley, University of Virginia
- Investigators
- Matthew Reilley, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07824960
- Sponsor's protocol ID
- 302740
- Acronym
- Panc 004
- Status last verified
- Sep 2026
- First submitted
- 2 Sep 2026
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No