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RecruitingNCT06648434Updated Apr 30, 2026

MK2 Inhibitor in Combination With mFOLFIRINOX for Untreated Metastatic Pancreatic Ductal Adenocarcinoma

A Phase 1 interventional study of Zunsemetinib and mFOLFIRINOX in Metastatic Pancreatic Ductal Adenocarcinoma, Pancreatic Cancer and Cancer of the Pancreas, sponsored by Washington University School of Medicine. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-30.

Sponsored by Washington University School of Medicine · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Started Jun 2025; still recruiting 1 year 3 months later.
Phase
Phase 1
Study type
Interventional
Enrollment
51
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The investigators hypothesize that MK2 inhibition may improve efficacy of mFOLFIRINOX chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC).

02

Conditions studied

  • Metastatic Pancreatic Ductal Adenocarcinoma
  • Pancreatic Cancer
  • Cancer of the Pancreas

Keywords

  • Pancreatic cancer
  • Zunsemetinib
  • FOLFIRINOX
03

In context

Pancreatic Neoplasms

3,235 studies on the registry are indexed under Pancreatic Neoplasms; 898 are open to participants now.

This study's planned enrollment of 51 is above the median of 46 across 2,424 interventional studies indexed under Pancreatic Neoplasms.

Browse Pancreatic Neoplasms studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.

Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.

  • 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).

Exclusion criteria

Exclusion Criteria:

  • 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.
  • 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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
51 participants (estimated)

Study arms

  • Experimental
    Dose escalation phase (zunsemetinib + mFOLFIRNOX)

    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.

    Drug: Zunsemetinib · Drug: mFOLFIRINOX

  • Experimental
    Dose expansion phase (zunsemetinib + mFOLFIRNOX)

    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.

    Drug: Zunsemetinib · Drug: mFOLFIRINOX

Interventions

  • DrugZunsemetinib

    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.

    Also known as: ATI-450

  • DrugmFOLFIRINOX

    Includes oxaliplatin, irinotecan, leucovorin, and 5-FU.

06

What researchers measure

Primary outcomes

  1. 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)

  2. 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)

Secondary outcomes

  1. Number of participants with adverse events by types

    Graded by CTCAE v5.

    Time frame: From start of treatment through 30 days after last zunsemetinib dose (estimated to be 13 months)

  2. 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.

    Time frame: At 6 months

  3. 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.

    Time frame: Through completion of treatment (estimated to be 12 months)

  4. 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.

    Time frame: Through completion of treatment (estimated to be 12 months)

  5. 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.

    Time frame: Through completion of follow-up (estimated to be 3 years)

  6. 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.

    Time frame: Through completion of follow-up (estimated to be 3 years)

  7. CA19-9 response rate (only for those treated at RP2D)

    Time frame: Through completion of treatment (estimated to be 12 months)

  8. 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)

07

Study locations

1 of 1 sites recruiting
  • Washington University School of Medicine
    St Louis, Missouri 63110, United States
    • Moh'd Khushman, M.D. · Contact · mkhushman@wustl.edu · 314-273-3564
    • Moh'd Khushman, M.D. · Principal investigator
    • Nikolaos Andreatos, M.D. · Sub investigator
    • Olivia Aranha, M.D., Ph.D. · Sub investigator
    • Patrick Grierson, M.D., Ph.D. · Sub investigator
    • Ramon Jin, M.D., Ph.D. · Sub investigator
    • Kian-Huat Lim, M.D., Ph.D. · Sub investigator
    • Rama Suresh, M.D. · Sub investigator
    • Benjamin Tan, M.D. · Sub investigator
    • Nikolaos Trikalinos, M.D. · Sub investigator
    • Max Wattenberg, M.D. · Sub investigator
    • Esther Lu, Ph.D. · Sub investigator
    • Chunjie Li, M.D., Ph.D. · Sub investigator
    • Mark O'Hara, M.D. · Sub investigator
    Recruiting
08

References and documents

Individual participant data

Plan to share: Yes — Individual patient data that underlie the results reported in the article, after deidentification (text, tables, figures, and appendices).

Supporting information: Study protocol, Sap, Analytic code

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 30, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06648434
Lead sponsor
Washington University School of Medicine
Collaborators
National Cancer Institute (NCI), Aclaris Therapeutics, Inc.
Responsible party
Sponsor
First posted
Oct 18, 2024
Start date
Jun 13, 2025
Primary completion
Jun 30, 2027 (estimated)
Completion
May 31, 2030 (estimated)
Last update
Apr 30, 2026

Study contacts

Moh'd Khushman, M.D.
Contact
mkhushman@wustl.edu
314-273-3564
Moh'd Khushman, M.D.
principal investigator · Washington University School of Medicine

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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