Phase 1b/2 Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced NSCLC (Substudy NSCLC)

Phase 1/2

Recruiting

• Conditions: Non-Small Cell Lung Cancer

• Registration Number: 2024-517818-15-00
• Lead Sponsor: Merck Healthcare KGaA

Brief Summary

To determine clinical activity in terms of Objective Response (OR) of M9140 monotherapy q3w.

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: 2025-09
• Last Update Submitted: 2025-09-25
• Last Update Posted: 2025-09-26
• Primary Completion: 2028-01-26
• Study Completion: 2028-01-26

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 51

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

Primary Outcome Measures

Name	Time	Method
Objective Response (OR) according to RECIST v1.1 as assessed by Investigators.		Objective Response (OR) according to RECIST v1.1 as assessed by Investigators.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events (AEs) and Treatment Related AEs.		Number of Participants with Adverse Events (AEs) and Treatment Related AEs.
Duration of Response (DoR) according to RECIST v1.1 as assessed by Investigators.		Duration of Response (DoR) according to RECIST v1.1 as assessed by Investigators.
Number of Participants with Disease Control.		Number of Participants with Disease Control.
Time to Response according to RECIST v1.1 as assessed by Investigators.		Time to Response according to RECIST v1.1 as assessed by Investigators.
Progression-free Survival (PFS) according to RECIST v1.1 as assessed by Investigators.		Progression-free Survival (PFS) according to RECIST v1.1 as assessed by Investigators.
Pharmacokinetic (PK) Plasma Concentrations of M9140.		Pharmacokinetic (PK) Plasma Concentrations of M9140.
Number of Participants with Anti-Drug Antibodies (ADA) against M9140.		Number of Participants with Anti-Drug Antibodies (ADA) against M9140.

Trial Locations

Locations (38)

University of California - Los Angeles - 300208353; 🇺🇸 Santa Monica, California, United States

Providence Medical Foundation; 🇺🇸 Santa Rosa, California, United States

Prisma Health Cancer Institute, ITOR, CRU; 🇺🇸 Greenville, South Carolina, United States

Baptist Memorial Health Care -Memphis; 🇺🇸 Memphis, Tennessee, United States

University of Texas M. D. Anderson Cancer Center - Partner; 🇺🇸 Houston, Texas, United States

NEXT Virginia; 🇺🇸 Fairfax, Virginia, United States

Flinders Medical Centre; 🇦🇺 Bedford Park, Australia

Nepean Cancer Care Centre; 🇦🇺 Kingswood, Australia

Mater Misericordiae Ltd - PARENT; 🇦🇺 South Brisbane, Australia

Macquarie University Hospital - PARENT; 🇦🇺 Sydney, Australia

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