Advanced Solid Tumor
Conditions
Keywords
Bispecific CD40 agonistic antibody, Mucin-1 (MUC-1), pembrolizumab, mFOLFIRINOX, pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC)
Brief summary
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
BIOLOGICALM0324
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).
BIOLOGICALPembrolizumab
Pembrolizumab will be administered intravenously as per standard of care.
DRUGmFOLFIRINOX
mFOLFIRINOX will be administered intravenously as per standard of care.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Parts 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs) | Day 1 up to Day 21 |
| Part 1, 2 and 3: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | Up to Month 40 |
| Part 3: Number of Participants With Dose Limiting Toxicities (DLTs) | Day 1 up to Day 35 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Parts 1 and 2: Pharmacokinetic (PK) Plasma Concentrations of M0324 | From Day 1 up to approximately 40 months | — |
| Parts 3: Pharmacokinetic (PK) Plasma Concentrations of M0324 | From Day 1 up to approximately 40 months | — |
| Percent Change from Baseline in Pharmacodynamic Markers | From Day 1 up to approximately 40 months | Pharmacodynamic and circulating biomarkers (e.g. cytokines) will be measured in blood. |
| Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator | 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 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 from first documentation of OR until progressive disease (PD) or death, assessed approximately up to 40 months | — |
| Part 3: Overall Survival (OS) | Time from first study treatment until death, assessed approximately up to 40 months | — |
| Number of Participants With Positive Anti-Drug Antibody (ADA) of M0324 | Up to Month 40 | — |
Countries
Canada, Japan, United States
Contacts
CONTACTUS Medical Information
CONTACTCommunication Center
STUDY_DIRECTORMedical Responsible
EMD Serono Research & Development Institute, Inc.
Outcome results
None listed