Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced Solid Tumors (PROCEADE PanTumor)

Phase 1

Recruiting

• Conditions: Solid Tumors; Pancreatic Cancer; Gastric Cancer; Pancreatic Ductal Adenocarcinoma (PDAC); Non-Small Cell Lung Cancer (NSCLC)
• Interventions: Drug: M9140

• Registration Number: NCT06710132
• Lead Sponsor: EMD Serono Research & Development Institute, Inc.

Brief Summary

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).

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.

Study Timeline

• Study First Submitted: 2024-11-22
• Study First Submitted QC: 2024-11-25
• Study First Posted: 2024-11-29
• Study Start: 2025-01-29
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-05
• Last Update Posted: 2025-05-07
• Primary Completion: 2029-01-31
• Study Completion: 2029-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Substudy NSCLC: M9140 Monotherapy - Part B CEACAM5 High EGFR mut	M9140	-
Substudy PDAC: M9140 Monotherapy - Part A CEACAM5 High	M9140	-
Substudy GC: M9140 Monotherapy - Part A CEACAM5 High	M9140	-
Substudy GC: M9140 Monotherapy - Part B CEACAM5 Low	M9140	-
Substudy NSCLC: M9140 Monotherapy - Part A CEACAM5 High EGFR Wt	M9140	-

Primary Outcome Measures

Name	Time	Method
Substudies GC/NSCLC/PDAC: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators	Time from first study treatment to (planned) final assessment at approximately 48 months

Secondary Outcome Measures

Name	Time	Method
Substudies GC/NSCLC/PDAC: Number of Participants with Adverse Events (AEs) and Treatment Related AEs	Time from first study treatment to (planned) final assessment at approximately 48 months
Substudies GC/NSCLC/PDAC: Number of Participants with Disease Control	At Week 12
Substudies GC/NSCLC/PDAC: Time to Response according to RECIST v1.1 as Assessed by Investigators	Time from first study treatment to (planned) final assessment at approximately 48 months
Substudies GC/NSCLC/PDAC: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators	Time from first study treatment to (planned) final assessment at approximately 48 months
Substudies GC/NSCLC/PDAC: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators	Time from first study treatment throughout the study duration until progressive disease or death due to any cause, whichever occur first, approximately 48 months
Substudies GC/ NSCLC/ PDAC: Pharmacokinetic (PK) Plasma Concentrations of M9140	Cycle (C) 1 Day (D) 1 to C3D15, C4D1 and from C8D1 every 4 cycles on D1 until treatment discontinuation (each cycle is of 21 days), assessed up to approximately 12 months
Substudies GC/NSCLC/PDAC: Number of Participants with Anti-Drug Antibodies (ADA) Against M9140	Predose (C1D1, C3D1, C8D1) and end of study intervention, assessed up to approximately 12 months
Substudy GC: CEACAM5 expression in tumor	Day 1

Trial Locations

Locations (4)

Saiseikai Kumamoto Hospital - 300175708; 🇯🇵 Kumamoto-shi, Japan

Kyungpook National University Chilgok Hospital; 🇰🇷 Daegu, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States