M0324 as Monotherapy and in Combination With Pembrolizumab or Chemotherapy in Participants With Selected Advanced Solid Tumors

Official title

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

Overview

The purpose of this first-in-human study is to identify a recommend dose(s) for subsequent larger studies (recommended dose(s) for expansion, RDE), examining increasing doses of M0324, primarily looking at safety, but also preliminary signs of efficacy, pharmacokinetics (PK), and pharmacodynamics (PD). Three different treatments with M0324 will be studied, M0324 as a monotherapy(Part 1), M0324 in combination with pembrolizumab (Part 2), and in combination with mFOLFIRINOX (a chemotherapy treatment)(Part 3).

Interventions

• Biological M0324
  M0324 will be tested at increasing doses as monotherapy to determine dose-toxicity relationship and MTD (if reached) in order to support selection of recommended dose(s) for expansion (RDE).
• Biological M0324
  M0324 will be further investigated in part 2 and part 3 of the study as combination regimen, in order to determine dose-toxicity relationship in combination and MTD (if reached) in order to support selection of RDE(s) in combination.
• Biological Pembrolizumab
  Pembrolizumab will be administered intravenously as per standard of care.
• Drug mFOLFIRINOX
  mFOLFIRINOX will be administered intravenously as per standard of care.

Primary outcome measures

• Parts 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs) [Time frame: Day 1 up to Day 21]
• Part 1, 2 and 3: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [Time frame: Up to Month 40]
• Part 3: Number of Participants With Dose Limiting Toxicities (DLTs) [Time frame: Day 1 up to Day 35]

Secondary outcome measures (8)

• Parts 1 and 2: Pharmacokinetic (PK) Plasma Concentrations of M0324 [Time frame: From Day 1 up to approximately 40 months]
• Parts 3: Pharmacokinetic (PK) Plasma Concentrations of M0324 [Time frame: From Day 1 up to approximately 40 months]
• Percent Change from Baseline in Pharmacodynamic Markers [Time frame: From Day 1 up to approximately 40 months]
• Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator [Time frame: Time from first study treatment until progressive disease or death up to approximately 40 months]
• Progression-Free Survival (PFS) Time Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Time frame: Time from first study treatment until first documentation of progressive disease (PD) or death, assessed approximately up to 40 months]
• Duration of Response (DoR) According to RECIST v1.1 as Assessed by Investigator [Time frame: Time from first documentation of OR until progressive disease (PD) or death, assessed approximately up to 40 months]
• Part 3: Overall Survival (OS) [Time frame: Time from first study treatment until death, assessed approximately up to 40 months]
• Number of Participants With Positive Anti-Drug Antibody (ADA) of M0324 [Time frame: Up to Month 40]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Yale University School of Medicine — New Haven
• Icahn School of Medicine at Mount Sinai — New York
• NEXT Oncology — San Antonio

Canada · 1 center

• Princess Margaret Cancer Centre — Toronto

Japan · 1 center

• National Cancer Center Hospital — Chūōku

Identifiers

NCT: NCT07166601 · MS201557_0009 · jRCT2031250509

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗