M0324 alone or with pembrolizumab or mFOLFIRINOX chemotherapy for selected advanced solid tumors

An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of M0324, a Bispecific (MUC-1 x CD40) Antibody as Monotherapy, in Combination With Pembrolizumab, and in Combination With Chemotherapy, in Participants With Selected Advanced Solid Tumors

This trial tests whether the experimental drug M0324, given alone or with pembrolizumab or mFOLFIRINOX chemotherapy, is safe and shows early signs of benefit for people with advanced solid tumors that overexpress MUC-1.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 77 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: EMD Serono (industry)
• Drugs / interventions: Pembrolizumab, chemotherapy
• Locations: 5 sites (New Haven, Connecticut and 4 other locations)
• Trial ID: NCT07166601 on ClinicalTrials.gov

What this trial studies

This first-in-human, phase 1 dose-escalation trial is studying increasing doses of M0324 as monotherapy and in two combination arms (with pembrolizumab and with mFOLFIRINOX) to identify recommended dose(s) for expansion. The primary focus is safety and tolerability, with secondary assessments of pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity. Part 1 enrolls patients with selected MUC-1–expressing advanced solid tumors refractory or intolerant to standard therapies; Part 2 enrolls similar patients who have progressed after prior immune checkpoint inhibitors; Part 3 enrolls patients with previously untreated metastatic pancreatic ductal adenocarcinoma eligible for mFOLFIRINOX. Dose escalation findings will determine doses and cohorts for later expansion.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced or metastatic solid tumors known to overexpress MUC-1 who are intolerant of or have progressed on standard therapies (for the pembrolizumab arm participants must have prior immune checkpoint inhibitor exposure and documented progression), with a separate cohort for previously untreated metastatic pancreatic adenocarcinoma eligible for mFOLFIRINOX.

Not a fit: Patients whose tumors do not overexpress MUC-1, those eligible for effective standard curative treatments, or those with comorbidities that preclude immunotherapy or intensive chemotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, M0324 could offer a new treatment option that activates the immune system against MUC-1–expressing tumors and possibly improve responses in hard-to-treat cancers such as pancreatic adenocarcinoma.

How similar studies have performed: Other early-phase trials of CD40 agonists and combinations with checkpoint inhibitors have shown immune activation and occasional responses, but M0324's bispecific MUC-1–CD40 approach is first-in-human and largely untested clinically.

Eligibility criteria

Inclusion Criteria:

Part 1- M0324 Monotherapy:

• Participants with certain advanced/metastatic solid tumor types known to overexpress MUC-1 and who are intolerant or refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator

Part 2- M0324 Combination with Pembrolizumab:

• Participants with certain advanced/metastatic tumor types known to overexpress MUC-1 and the participants in the combination treatment involving M0324 and pembrolizumab must be intolerant or refractory to standard therapy and no other further standard therapy should be judged appropriate by the Investigator. In addition, the participants must have had prior treatment with immune checkpoint inhibitor(s) (ICIs) and must have experienced documented disease progression on or after ICIs.

Part 3- M0324 Combination with mFOLFIRINOX:

* Participants with previously untreated metastatic pancreatic ductal adenocarcinoma, who are judged by Investigator as eligible for treatment with mFOLFIRINOX. Participants with prior Whipple surgery and/or adjuvant chemotherapy are not permitted
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Has a history of chronic diarrhea greater than or equal to (\>=) Grade 2, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
* Participant has a history of malignancy within 3 years before the date of enrollment
* Uncontrolled or poorly controlled arterial hypertension, uncontrolled cardiac arrhythmia, unstable angina, myocardial infarction, congestive heart failure \[New York Heart Association (NYHA) \>= II\] or a coronary revascularization procedure within 180 days of study entry
* Life expectancy of less than 3 months
* Other protocol defined exclusion criteria could apply

Where this trial is running

New Haven, Connecticut and 4 other locations

• Yale University School of Medicine — New Haven, Connecticut, United States (RECRUITING)
• Icahn School of Medicine at Mount Sinai — New York, New York, United States (NOT_YET_RECRUITING)
• NEXT Oncology — San Antonio, Texas, United States (RECRUITING)
• Princess Margaret Cancer Centre — Toronto, Canada (RECRUITING)
• National Cancer Center Hospital — Chūōku, Japan (RECRUITING)

Study contacts

• Study coordinator: US Medical Information

Conditions: Advanced Solid Tumor, Bispecific CD40 agonistic antibody, Mucin-1, pembrolizumab, mFOLFIRINOX, pancreatic ductal adenocarcinoma, non-small cell lung cancer