Phase 1b/2 Study of Anti-CEACAM5 ADC Precemtabart Tocentecan (M9140) in Participants With Advanced Gastric Cancer (Substudy GC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Healthcare KGaA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Jun 2025 → ongoing

Decision date (initial)

2025-05-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Merck Healthcare KGaA

External identifiers

EU CT number

2024-517817-34-00

ClinicalTrials.gov

NCT06710132

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

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

Secondary objectives 7

1. To determine safety and tolerability of M9140.
2. To determine clinical activity in terms of Duration of Response (DoR) of M9140 monotherapy q3w.
3. To evaluate Disease Control (DC) at 12 weeks in M9140 monotherapy q3w.
4. To evaluate indicators of clinical activity of M9140 in terms of Time to Response using RECIST v1.1.
5. To evaluate indicators of clinical activity of M9140 in terms of Progression-free Survival (PFS) using RECIST v1.1.
6. To characterize the Pharmacokinetic (PK) profile of M9140.
7. To evaluate CEACAM5 expression cutoff point for patient selection for future studies.

Conditions and MedDRA coding

Gastric Cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participants are capable of signing informed consent as defined in protocol.
2. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤1.
3. Participants with adequate hematologic, hepatic and renal function as defined in protocol.
4. Participant must have at least 1 lesion that is measurable using RECIST v1.1.
5. Participants in Part A and Part B with documented histopathological diagnosis of advanced or metastatic, HER2 negative, gastric or GEJ adenocarcinoma, who were intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage.
6. Participants must have received and progressed (according to RECIST v1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2.
7. Participants in Part A with CEACAM5high GC/GEJC (defined as IHC ≥ 2+ staining in ≥ 50% of tumor cells).
8. Participants in Part B with CEACAM5low GC/GEJC (defined as IHC ≥ 2+ staining in < 50% of tumor cells).

Exclusion criteria 7

1. 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).
2. 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).
3. Participants with diarrhea (liquid stool) or ileus Grade > 1.
4. Participants with active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease, intestinal perforation) and/or bowel obstruction.
5. 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).
6. Cerebrovascular accident/stroke (< 6 months prior to enrollment).
7. Participants with prior therapy with irinotecan.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 8

1. Number of Participants with Adverse Events (AEs) and Treatment Related AEs.
2. Duration of Response (DoR) according to RECIST v1.1 as assessed by Investigators.
3. Number of Participants with Disease Control.
4. Time to Response according to RECIST v1.1 as assessed by Investigators.
5. Progression-free Survival (PFS) according to RECIST v1.1 as assessed by Investigators.
6. Pharmacokinetic (PK) Plasma Concentrations of M9140.
7. Number of Participants with Anti-Drug Antibodies (ADA) against M9140.
8. CEACAM5 expression in tumor.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Healthcare KGaA

Sponsor organisation

Merck Healthcare KGaA

Address

Frankfurter Strasse 250

City

Darmstadt

Postcode

64293

Country

Germany

Scientific contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Third parties 11

Locations

5 EU/EEA countries · 35 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 63 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications