Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced Solid Tumors (PROCEADE PanTumor)
Purpose
The PROCEADE PanTumor study aims to investigate M9140 in multiple tumor types which express carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and it is therefore designed as a matrix study. This study aims to assess the antitumor activity, tolerability, safety, and pharmacokinetics (PK) of M9140 as monotherapy or in combination treatments in adult participants with locally advanced/metastatic CEACAM5 expressing tumors. There will be 3 substudies under this Master Protocol that may be conducted in parallel. - PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Gastric Cancer (Substudy GC); - PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants with Advanced Non-Small Cell Lung Cancer (Substudy NSCLC); - PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants With Advanced Pancreatic Cancer (Substudy PDAC).
Conditions
- Solid Tumors
- Gastric Cancer
- Non-Small Cell Lung Cancer (NSCLC)
- Pancreatic Cancer
- Pancreatic Ductal Adenocarcinoma (PDAC)
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Participants are capable of signing informed consent as defined in protocol - Eastern Cooperative Oncology Group Performance Status (ECOG PS) below or equal to 1 - Participants with adequate hematologic, hepatic and renal function as defined in protocol - Participant must have at least 1 lesion that is measurable using RECIST v1.1. - Other protocol defined inclusion criteria could apply Substudy GC: - Participants in Part A and Part B with documented histopathological diagnosis of advanced or metastatic, HER2 negative, gastric or GEJ (with an epicenter 2 centimeter (cm) proximal or distal to the GEJ) adenocarcinoma, who were intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage that must have included (provided there is no medical contraindication and these agents are locally approved and available) a fluoropyrimidine and a platinum agent and an Immune checkpoint inhibitors (ICI) for participants with a known microsatellite instability-high (MSI-H) status or participants whose tumor express PD-L1 with a CPS greater than or equal (>=) 1 - Participants must have received and progressed (according to RECIST 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2 - Participants in Part A with CEACAM5high GC/GEJC (defined as IHC >= 2+ staining in >= 50% of tumor cells) - Participants in Part B with CEACAM5low GC/GEJC (defined as IHC >= 2+ staining in less than (<) 50% of tumor cells) - Other protocol defined inclusion criteria could apply Substudy NSCLC: - Participants in Part A and Part B with histologically or cytologically documented advanced (Stage III not eligible for resection or curative radiation) or metastatic NSCLC with or without driver genomic alterations - Participants must have been intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage - Participants must have received and progressed (according to RECIST 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 3 - Participants who received a platinum-containing regimen or a targeted therapy as (neo)-adjuvant therapy for early-stage disease, if relapse or metastases occurred during or within 3 months after regimen completion, are considered to have received a line of treatment in the advanced setting - Participants in Part A with CEACAM5 high-expressing EGFR tumors (including participants with any driver genomic alterations other than EGFR mutations - Participants in Part B with CEACAM5 high known EGFR mutated tumors as assessed according to local clinical practice - Other protocol defined inclusion criteria could apply Substudy PDAC: - Participants with histologically or cytologically confirmed advanced or metastatic PDAC, who were intolerant/refractory to or progressed after systemic therapies for the advanced metastatic stage that must have included (provided there is no medical contraindications, and these agents are locally approved and available; FOLFIRINOX regimen or NALIRIFNOX regimen or Nab-paclitaxel/gemcitabine regimen - Participants must have received and progressed (according to RECIST 1.1) on at least one 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2 - All participants will be screened using an IHC test to define CEACAM5 expression. Only participants with CEACAM5high expressing tumors will be eligible - Other protocol defined inclusion criteria could apply
Exclusion Criteria
- Participant has a history of malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years) - Participants with known brain metastases, except those meeting the following criteria: Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment; No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) - Participants with diarrhea (liquid stool) or ileus Grade > 1 - Participants with active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, intestinal perforation) and/or bowel obstruction - 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. Calculated QTc average (using the Fridericia correction calculation) of > 470 milliseconds (ms) - Cerebrovascular accident/stroke (< 6 months prior to enrollment) - Other protocol defined exclusion criteria could apply Substudy GC - Participants with prior therapy with irinotecan Substudy NSCLC: - Participants with prior therapy with irinotecan Substudy PDAC: none
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
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Experimental Substudy GC: M9140 Monotherapy - Part A CEACAM5 High |
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Experimental Substudy GC: M9140 Monotherapy - Part B CEACAM5 Low |
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Experimental Substudy NSCLC: M9140 Monotherapy - Part A CEACAM5 High EGFR Wt |
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Experimental Substudy NSCLC: M9140 Monotherapy - Part B CEACAM5 High EGFR mut |
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Experimental Substudy PDAC: M9140 Monotherapy - Part A CEACAM5 High |
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Recruiting Locations
Washington D.C. 4140963, District of Columbia 4138106 20007
More Details
- Status
- Recruiting
- Sponsor
- EMD Serono Research & Development Institute, Inc.
Detailed Description
The study follows a master protocol concept with several separate substudies in specific indications. - Substudy GC: The study duration per participant is on an average approximately 10 months. This includes a 28-day Screening period, infusion (approximately 1 hour) on Day 1 of every cycle, and Safety Follow-up Visit 30 (± 3) days after the last dose of M9140. - Substudy NSCLC: Study duration per participant is approximately 12 months. This includes a 28-day Screening period, infusion (approximately 1 hour) on Day 1 of every cycle, and Safety Follow-up Visit 30 (± 3) days after the last dose of M9140. - Substudy PDAC: Study duration per participant is on an average approximately 8 months. This includes a 28-day Screening period, infusion (approximately 1 hour) on Day 1 of every cycle, and Safety Follow-up Visit 30 (±3) days after the last dose of M9140.