Metastatic Pancreatic Ductal AdenocarcinomaPhase 1NCT06648434
MK2 Inhibitor in Combination With mFOLFIRINOX for Untreated Metastatic Pancreatic Ductal Adenocarcinoma
A Phase 1 study testing Zunsemetinib and mFOLFIRINOX in people with Metastatic Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The investigators hypothesize that MK2 inhibition may improve efficacy of mFOLFIRINOX chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer, Cancer of the Pancreas
- What is being tested?
- Zunsemetinib and mFOLFIRINOX
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2025to 31 May 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Histologically or cytologically confirmed pancreatic ductal adenocarcinoma with no prior systemic treatment for advanced or metastatic disease. Patients with mixed cytology in their tumors such as adeno-squamous, mixed neuroendocrine-carcinoma are permitted if the portion of adenocarcinoma is predominant. Prior adjuvant/neoadjuvant therapy (including FOLFIRINOX or mFOLFIRINOX regimens) is allowed if progression occurred ≥ 12 months from the last dose of that therapy. A biopsy is not required to confirm advanced or metastatic disease.
- Dose escalation: Diagnosis of advanced inoperable or metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is deemed a suitable option per the treating physician.
- Dose expansion: Diagnosis of metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is deemed a suitable option per the treating physician.
- Measurable disease by RECIST 1.1.
- At least 18 years of age
- ECOG performance status ≤ 1.
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- Adequate bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm without transfusion within 2 weeks prior to C1D1
- Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks prior to C1D1
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN, unless there are liver metastases in which case AST and ALT ≤ 5.0 x IULN
- Creatinine clearance > 50 mL/min by Cockcroft-Gault
- Baseline EKG with QTcF ≤ 460 ms.
- Women of childbearing potential and men who are heterosexually active must agree to use adequate contraception as specified in the protocol. Contraception should continue for 1 month following last dose of zunsemetinib, 6 months following last dose of irinotecan, 9 months following last dose of oxaliplatin, and/or 3 months following last dose of fluorouracil. Should a woman (or the female partner of a male participant) become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- A history of other malignancy with the exception of 1) malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease; 2) or known indolent malignancies that do not require treatment and will likely not alter the course of treatment of metastatic pancreatic cancer.
- History of allogeneic organ or stem cell transplant.
- Currently receiving any other investigational agents, or receipt of an investigational agent within 2 weeks or 5 half-lives of the agent, whichever is shorter.
- Receipt of strong and moderate CYP3A4 and CYP2C8 inhibitors (including grapefruit), strong and moderate CYP3A and CYP2C8 inducers (see Appendices H and I), and drugs with QT prolonging potential within 5 half-lives of cycle 1 day 1.
- Known brain metastases or CNS involvement, because brain metastases are often associated with poor functional status, shortened life expectancy and risk of toxicity.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to zunsemetinib, or other agents used in the study.
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- Clinically significant neuropathy ≥ grade 2.
- Presence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.
- Gastrointestinal conditions which could prevent absorption of zunsemetinib, in the opinion of the treating physician.
- Inability to swallow pills.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia .
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 7 days of C1D1.
- Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.
- Major surgery within 28 days prior to C1D1. Major surgery refers to any surgical procedure that involves general or regional anesthesia, involves extensive resecting or altering of body parts, carries a higher risk of complications, or requires long recovery times. Central line placement is allowed.
- Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of C1D1.
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, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Moh'd Khushman, M.D., 314-273-3564, mkhushman@wustl.edu
Moh'd Khushman, M.D.
About this study
Official title: Phase I Trial of MK2 Inhibitor in Combination With mFOLFIRINOX for Untreated Metastatic Pancreatic Ductal Adenocarcinoma
The investigators hypothesize that MK2 inhibition may improve efficacy of mFOLFIRINOX chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC).
- Being tested
- Zunsemetinib, mFOLFIRINOX
- Keywords
- Pancreatic cancer, Zunsemetinib, FOLFIRINOX
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZunsemetinibDrug
Also called ATI-450
Patients should take zunsemetinib approximately 12 hours apart (if twice daily dosing) or 24 hours apart (if once daily dosing) at the same time(s) every day, with 8 oz of water.
mFOLFIRINOXDrug
Includes oxaliplatin, irinotecan, leucovorin, and 5-FU.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation phase (zunsemetinib + mFOLFIRNOX) | Experimental | The dose of zunsemetinib will be determined by the dose level assigned and will be taken by mouth either once or twice daily depending on assigned dose level. mFOLFIRINOX will be 85 mg/m^2 of oxaliplatin intravenous (IV) on day 1 of each cycle, 150 mg/m^2 of irinotecan IV on day 1 of each cycle, 400 mg/m^2 of leucovorin IV on day 1 of each cycle, and 2400 mg/m^2 continuous infusion starting on day 1 of each cycle and continuing for 46 hours. Each cycle is 2 weeks in length. Receives: Drug: Zunsemetinib; Drug: mFOLFIRINOX |
| Dose expansion phase (zunsemetinib + mFOLFIRNOX) | Experimental | The dose of zunsemetinib will be determined during the dose escalation phase of the trial. mFOLFIRINOX will be 85 mg/m^2 of oxaliplatin intravenous (IV) on day 1 of each cycle, 150 mg/m^2 of irinotecan IV on day 1 of each cycle, 400 mg/m^2 of leucovorin IV on day 1 of each cycle, and 2400 mg/m^2 continuous infusion starting on day 1 of each cycle and continuing for 46 hours. Each cycle is 2 weeks in length. Receives: Drug: Zunsemetinib; Drug: mFOLFIRINOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose (RP2D) of zunsemetinib in combination with mFOLFIRINOX (Dose Escalation Only)
Measured: Completion of 2 cycles (each cycle is 2 weeks - estimated to be 4 weeks)
Number of participants with dose-limiting toxicities (DLTs) (Dose Escalation only)
Measured: Completion of 2 cycles (each cycle is 2 weeks - estimated to be 4 weeks)
Secondary outcomes (8)
Number of participants with adverse events by types
Graded by CTCAE v5.
Measured: From start of treatment through 30 days after last zunsemetinib dose (estimated to be 13 months)
Progression-free rate (PFR) (only for those treated at RP2D)
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and/or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: At 6 months
Disease control rate (DCR) (only for those treated at RP2D)
DCR is defined as the number of participants with complete response, partial response, or stable disease) per RECIST 1.1.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and disappearance of all non-target lesions and normalization of tumor marker level.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Through completion of treatment (estimated to be 12 months)
Overall response rate (ORR) (only for those treated at RP2D)
ORR = defined as number of participants with complete response or partial response by RECIST 1.1.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and disappearance of all non-target lesions and normalization of tumor marker level.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Through completion of treatment (estimated to be 12 months)
Progression-free survival (PFS) (only for those treated at RP2D)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and/or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: Through completion of follow-up (estimated to be 3 years)
Overall survival (OS) (only for those treated at RP2D)
OS is defined as the duration of time from start of treatment to time of death from any cause.
Measured: Through completion of follow-up (estimated to be 3 years)
CA19-9 response rate (only for those treated at RP2D)
Measured: Through completion of treatment (estimated to be 12 months)
Change in plasma concentration of zunsemetinib and its metabolites
Measured: Cycle 1 day 1 (each cycle is 2 weeks), cycle 2 day 1 (each cycle is 2 weeks), cycle 3 day 1 (each cycle is 2 weeks), cycle 4 day 1 (each cycle is 2 weeks), and end of treatment (estimated to be 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start13 Jun 2025
- Primary completion30 Jun 2027 (estimated)
- Study completion31 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Aclaris Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Moh'd Khushman, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06648434
- Sponsor's protocol ID
- 202502144
- Other IDs
- P50CA272213
- Status last verified
- Apr 2026
- First submitted
- 15 Oct 2024
- Last updated
- 30 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual patient data that underlie the results reported in the article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of MK2 Inhibitor in Combination With mFOLFIRINOX for Untreated Metastatic Pancreatic Ductal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT06648434
- Acronym / sponsor ID
- 202502144
- Keywords
- Pancreatic cancer, Zunsemetinib, FOLFIRINOX
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Aclaris Therapeutics, Inc.
- Study start
- 13 Jun 2025 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 May 2030 (estimated)
- First posted
- 18 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that MK2 inhibition may improve efficacy of mFOLFIRINOX chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose escalation phase (zunsemetinib + mFOLFIRNOX) | Experimental | Drug: Zunsemetinib, Drug: mFOLFIRINOXThe dose of zunsemetinib will be determined by the dose level assigned and will be taken by mouth either once or twice daily depending on assigned dose level. mFOLFIRINOX will be 85 mg/m^2 of oxaliplatin intravenous (IV) on day 1 of each cycle, 150 mg/m^2 of irinotecan IV on day 1 of each cycle, 400 mg/m^2 of leucovorin IV on day 1 of each cycle, and 2400 mg/m^2 continuous infusion starting on day 1 of each cycle and continuing for 46 hours. Each cycle is 2 weeks in length. |
| Dose expansion phase (zunsemetinib + mFOLFIRNOX) | Experimental | Drug: Zunsemetinib, Drug: mFOLFIRINOXThe dose of zunsemetinib will be determined during the dose escalation phase of the trial. mFOLFIRINOX will be 85 mg/m^2 of oxaliplatin intravenous (IV) on day 1 of each cycle, 150 mg/m^2 of irinotecan IV on day 1 of each cycle, 400 mg/m^2 of leucovorin IV on day 1 of each cycle, and 2400 mg/m^2 continuous infusion starting on day 1 of each cycle and continuing for 46 hours. Each cycle is 2 weeks in length. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically or cytologically confirmed pancreatic ductal adenocarcinoma with no prior systemic treatment for advanced or metastatic disease. Patients with mixed cytology in their tumors such as adeno-squamous, mixed neuroendocrine-carcinoma are permitted if the portion of adenocarcinoma is predominant. Prior adjuvant/neoadjuvant therapy (including FOLFIRINOX or mFOLFIRINOX regimens) is allowed if progression occurred ≥ 12 months from the last dose of that therapy. A biopsy is not required to confirm advanced or metastatic disease.
- Dose escalation: Diagnosis of advanced inoperable or metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is deemed a suitable option per the treating physician.
- Dose expansion: Diagnosis of metastatic disease, where mFOLFIRINOX (or classical FOLFIRINOX) is deemed a suitable option per the treating physician.
- Measurable disease by RECIST 1.1.
- At least 18 years of age
Key exclusion criteria (15 listed)
- A history of other malignancy with the exception of 1) malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease; 2) or known indolent malignancies that do not require treatment and will likely not alter the course of treatment of metastatic pancreatic cancer.
- History of allogeneic organ or stem cell transplant.
- Currently receiving any other investigational agents, or receipt of an investigational agent within 2 weeks or 5 half-lives of the agent, whichever is shorter.
- Receipt of strong and moderate CYP3A4 and CYP2C8 inhibitors (including grapefruit), strong and moderate CYP3A and CYP2C8 inducers (see Appendices H and I), and drugs with QT prolonging potential within 5 half-lives of cycle 1 day 1.
- Known brain metastases or CNS involvement, because brain metastases are often associated with poor functional status, shortened life expectancy and risk of toxicity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZunsemetinibAlso: ATI-450Patients should take zunsemetinib approximately 12 hours apart (if twice daily dosing) or 24 hours apart (if once daily dosing) at the same time(s) every day, with 8 oz of water. | Drug | Dose escalation phase (zunsemetinib + mFOLFIRNOX), Dose expansion phase (zunsemetinib + mFOLFIRNOX) |
| mFOLFIRINOXIncludes oxaliplatin, irinotecan, leucovorin, and 5-FU. | Drug | Dose escalation phase (zunsemetinib + mFOLFIRNOX), Dose expansion phase (zunsemetinib + mFOLFIRNOX) |
Primary outcome
Recommended phase II dose (RP2D) of zunsemetinib in combination with mFOLFIRINOX (Dose Escalation Only)
Time frame: Completion of 2 cycles (each cycle is 2 weeks - estimated to be 4 weeks)
Number of participants with dose-limiting toxicities (DLTs) (Dose Escalation only)
Time frame: Completion of 2 cycles (each cycle is 2 weeks - estimated to be 4 weeks)
8 secondary outcomes
Number of participants with adverse events by types
Time frame: From start of treatment through 30 days after last zunsemetinib dose (estimated to be 13 months)
Progression-free rate (PFR) (only for those treated at RP2D)
Time frame: At 6 months
Disease control rate (DCR) (only for those treated at RP2D)
Time frame: Through completion of treatment (estimated to be 12 months)
Overall response rate (ORR) (only for those treated at RP2D)
Time frame: Through completion of treatment (estimated to be 12 months)
Progression-free survival (PFS) (only for those treated at RP2D)
Time frame: Through completion of follow-up (estimated to be 3 years)
Overall survival (OS) (only for those treated at RP2D)
Time frame: Through completion of follow-up (estimated to be 3 years)
CA19-9 response rate (only for those treated at RP2D)
Time frame: Through completion of treatment (estimated to be 12 months)
Change in plasma concentration of zunsemetinib and its metabolites
Time frame: Cycle 1 day 1 (each cycle is 2 weeks), cycle 2 day 1 (each cycle is 2 weeks), cycle 3 day 1 (each cycle is 2 weeks), cycle 4 day 1 (each cycle is 2 weeks), and end of treatment (estimated to be 12 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual patient data that underlie the results reported in the article, after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Moh'd Khushman, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zunsemetinib and mFOLFIRINOX in people with Metastatic Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Moh'd Khushman, M.D. (314-273-3564, mkhushman@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase II dose (RP2D) of zunsemetinib in combination with mFOLFIRINOX (Dose Escalation Only) (time frame: Completion of 2 cycles (each cycle is 2 weeks - estimated to be 4 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2026.