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

PROCEADE PanTumor: A Phase 1b/2, Multicenter, Open-Label Study of Anti-CEACAM5 Antibody-Drug Conjugate M9140 in Participants With Advanced Solid Tumors (Master Protocol)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric Cancer; Pancreatic Cancer; Solid Tumors; Non-Small Cell Lung Cancer (NSCLC); Pancreatic Ductal Adenocarcinoma (PDAC)
• Intervention / Treatment: Drug: M9140

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 Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia
    • Flinders Medical Centre
  • Kingswood, Australia
    • Nepean Cancer Care Centre
  • South Brisbane, Australia
    • Mater Misericordiae Ltd - PARENT
  • Sydney, Australia
    • Macquarie University Hospital - PARENT
• Austria
  • Linz, Austria
    • Ordensklinikum Linz Krankenhaus der Elisabethinen Linz - Pneumology
  • Salzburg, Austria
    • LKH - Universitätsklinikum der PMU Salzburg - Innere Med III/Hämatologie und Onkologie
  • Vienna, Austria, 1090
    • Medical University of Vienna - Department of Internal Medicine
• China
  • Anhui
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510060
      • Sun Yat-sen University Cancer Center
  • Hebei
    • Wuhan, Hebei, China, 430021
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital
  • Hu'nan
    • Changsha, Hu'nan, China, 410000
      • Xiangya Hospital, Central South University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
  • Sichuan
    • Chengdu, Sichuan, China, 610176
      • Sichuan Cancer hospital
    • Chengdu, Sichuan, China, 611100
      • West China Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 156022
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine - Department of Oncology Surgery
• France
  • Bordeaux, France
    • Institut Bergonié - Service d'Oncologie Médicale
  • Dijon, France
    • Centre Georges François Leclerc - Unité de Phase I
  • Lille, France
    • Centre Oscar Lambret - cancerologie generale
  • Lille, France
    • Hopital Albert Calmette - CHU Lille - CHU Lille - Institut Coeur Poumon
  • Paris, France
    • Hôpital Européen Georges Pompidou - Hématologie Oncologie
  • Paris, France
    • Hôpital Saint-Antoine - Oncologie Médicale
  • Saint-Herblain, France
    • ICO - Site René Gauducheau - Service d'Oncologie medicale
  • Suresnes, France
    • Hôpital Foch - Service d'Oncologie Médicale
  • Toulouse, France
    • Institut Claudius Regaud - Service d'oncologie médicale
  • Villejuif, France
    • Institut Gustave Roussy - Pathologie Thoracique
• Germany
  • Berlin, Germany, 10117
    • Charité - Campus Charité Mitte - Charité Comprehensive Cancer Center
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60488
      • Krankenhaus Nordwest GmbH - Neurologische Klinik
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44791
      • St. Josef-Hospital im Katholischen Klinikum Bochum - Haematologie, Onkologie und Palliativmedizin
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - I. Medizinische Klinik Gastroenterologie u Hepato.
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus TU Dresden - Medizinische Klinik I
    • Leipzig, Saxony, Germany, 04103
      • Universitaetsklinikum Leipzig AoeR - Universitaeres Krebszentrum Leipzig (UCCL)
• Italy
  • Ancona, Italy, 60100
    • Azienda Ospedaliero Universitaria Ospedali Riuniti - UOC Clinica di Oncologia Medica
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale Dei Tumori
  • Milan, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda) - Struttura Complessa di Oncologia Falck
  • Naples, Italy, 80131
    • Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli" - Dipartimento di Oncologia
  • Padova, Italy, 35128
    • IOV - Istituto Oncologico Veneto IRCCS - S.Semplice Dip.Oncologia dei Melanomi
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia II
  • Reggio Emilia, Italy
    • Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia - Servizio di Oncologia
  • Roma, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Dipartimento di Medicina Interna e Scienze Mediche
  • Roma
    • Rome, Roma, Italy, 00144
      • Istituto Nazionale Tumori Regina Elena IRCCS - S.C. Oncologia Medica B
• Japan
  • Chūōku, Japan
    • National Cancer Center Hospital
  • Kashihara-shi, Japan
    • Nara Medical University Hospital - Dept of Oncology
  • Kumamoto, Japan
    • Saiseikai Kumamoto Hospital - 300175708
  • Kurume-shi, Japan
    • Kurume University Hospital
  • Kōtoku, Japan
    • Cancer Institute Hospital of JFCR
  • Niigata, Japan
    • Niigata Cancer Center Hospital - 300176282
  • Osakasayama-shi, Japan
    • Kindai University Hospital
  • Sapporo, Japan
    • NHO Hokkaido Cancer Center - 300175802
• South Korea
  • Busan, South Korea
    • Pusan National University Hospital
  • Daegu, South Korea
    • Kyungpook National University Chilgok Hospital
  • Seongnam, South Korea
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Korea University Guro Hospital
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea
    • Severance Hospital, Yonsei University Health System - Division of Infectious Diseases
  • Jeollanam-do
    • Hwasun-gun, Jeollanam-do, South Korea, 58128
      • Chonnam National University Hwasun Hospital
• Spain
  • Badalona, Spain
    • ICO Badalona - Hospital Universitari Germans Trias i Pujol - Servicio de Oncologia Medica
  • Barcelona, Spain
    • Hospital HM Nou Delfos - START Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron - Oncology Dept.
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona - Servicio de Oncologia
  • L'Hospitalet de Llobregat, Spain
    • ICO l'Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal - Servicio de Oncologia
  • Madrid, Spain
    • Centro Integral Oncologico Clara Campal - Unidad de Fase I-Oncologica
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Diaz - START Madrid FJD - Oncology Phase I
  • Pozuelo de Alarcón, Spain
    • NEXT Madrid - Hospital Universitario Quironsalud Madrid
  • Seville, Spain, 41014
    • Hospital Universitario Virgen de Valme
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena - Oncology Service
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe - Oncology Department
  • Córdoba
    • Córdoba, Córdoba, Spain, 14004
      • Hospital Universitario Reina Sofia - Dept of Oncology
• United States
  • California
    • Santa Monica, California, United States, 90404
      • University of California - Los Angeles - 300208353
    • Santa Rosa, California, United States, 95403
      • Providence Medical Foundation
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University - Lombardi Comprehensive Cancer Center - 1134847
  • Florida
    • Margate, Florida, United States, 33063
      • D&H Cancer Research Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute, ITOR, CRU
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Substudy GC: M9140 Monotherapy - Part A CEACAM5 High	Drug: M9140; All participants will receive 2.8 milligram per kilogram (mg/kg) M9140 intravenously (i.v.) every 3 weeks (q3w) on Day 1 of consecutive 21-day cycles.; Other Names: Precemtabart tocentecan
Experimental: Substudy GC: M9140 Monotherapy - Part B CEACAM5 Low	Drug: M9140; All participants will receive 2.8 milligram per kilogram (mg/kg) M9140 intravenously (i.v.) every 3 weeks (q3w) on Day 1 of consecutive 21-day cycles.; Other Names: Precemtabart tocentecan
Experimental: Substudy NSCLC: M9140 Monotherapy - Part A CEACAM5 High EGFR Wt	Drug: M9140; All participants will receive 2.8 milligram per kilogram (mg/kg) M9140 intravenously (i.v.) every 3 weeks (q3w) on Day 1 of consecutive 21-day cycles.; Other Names: Precemtabart tocentecan
Experimental: Substudy NSCLC: M9140 Monotherapy - Part B CEACAM5 High EGFR mut	Drug: M9140; All participants will receive 2.8 milligram per kilogram (mg/kg) M9140 intravenously (i.v.) every 3 weeks (q3w) on Day 1 of consecutive 21-day cycles.; Other Names: Precemtabart tocentecan
Experimental: Substudy PDAC: M9140 Monotherapy - Part A CEACAM5 High	Drug: M9140; All participants will receive 2.8 milligram per kilogram (mg/kg) M9140 intravenously (i.v.) every 3 weeks (q3w) on Day 1 of consecutive 21-day cycles.; Other Names: Precemtabart tocentecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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: 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: 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: 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

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany; Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2025
• Primary Completion (Estimated): December 23, 2027
• Study Completion (Estimated): December 23, 2027

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 25, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Gastric Cancer; Pancreatic Cancer; Solid Tumors; Gastroesophageal junction cancer; ADC; TOP1 inhibitor
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: MS202329_0010; 2024-517817-34-00 (Other Identifier: CTIS); 2024-517818-15-00 (Other Identifier: CTIS); 2024-517819-74-00 (Other Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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 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
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No