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

Study Identifier:
MS202329-0010
CT.gov Identifier:
NCT06710132
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
2024-517817-34-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

The aim of the study is 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.

The PROCEADE PanTumor study aims to study the clinical activity of M9140 in multiple CEACAM5-positive tumor types, so a matrix study design is used. It aims to evaluate the anti-tumor activity, tolerability, safety and PK of M9140 monotherapy or combined with other anti-tumor treatments in adult subjects with CEACAM5-positive advanced solid tumors. Based on the main protocol, this study is divided into three sub-studies according to indications and carried out simultaneously.

To investigate the clinical activity of precemtabart tocentecan, either as monotherapy or in combination with other anticancer agents, in patients with advanced GC, advanced NSCLC and advanced PDAC.

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

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
  • Gastric
  • Non-Small Cell Lung Cancer
  • Pancreas
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Substudy GC: M9140 Monotherapy - Part A CEACAM5 HighDrug: M9140
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  • Drug: Experimental: Substudy GC: M9140 Monotherapy - Part B CEACAM5 LowDrug: M9140
  • Drug: Experimental: Substudy NSCLC: M9140 Monotherapy - Part A CEACAM5 High EGFR WtDrug: M9140
  • Drug: Experimental: Substudy NSCLC: M9140 Monotherapy - Part B CEACAM5 High EGFR mutDrug: M9140
  • Drug: Experimental: Substudy PDAC: M9140 Monotherapy - Part A CEACAM5 HighDrug: M9140
  • Drug: Experimental Drugs
  • Drug: CTIS:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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
    • 1 The principal research is able to comply with the requirements outlined in the ICF and this protocol.
    • 2 ECOG performance status ≤ 1.
    • 3 Participants with normal hematologic, hepatic, and renal function as defined in the protocol were eligible.
    • 4 Participants were required to have at least one lesion measurable using RECIST v1.1.
    • 5 All other inclusion criteria defined in the protocol also needed to be met.
    • 6 Sub-study Gastric Cancer Part A and Part B: Subjects with documented histopathological diagnosis of advanced or metastatic, HER2-negative, gastric or GEJ (tumor epicenter within 2 cm proximal or distal to the GEJ) adenocarcinoma who are intolerant/refractory to or have disease progression following systemic therapy for advanced/metastatic disease, which must include the following treatments (provided there are no medical contraindications and the drugs are approved and available locally): fluoropyrimidines and platinum drugs. ICIs (subjects with known MSI-H status or subjects whose tumors express PD-L1 and have a CPS ≥ 1).
    • 7 Participants must have had disease progression after at least one line of therapy (according to RECIST 1.1), but no more than two lines of therapy.
    • 8 Part A: Subjects with CEACAM5-high GC/GEJC (defined as IHC staining intensity ≥2+ in ≥50% of tumor cells).
    • 9 Part B: Subjects with CEACAM5-low expressing GC/GEJC (defined as IHC staining intensity ≥ 2+ in <50% of tumor cells).
    • 10 All other inclusion criteria defined in the protocol also needed to be met.
    • 11 Sub-study Lung Cancer Part A and B: Participants have histologically or cytologically confirmed advanced (stage III, not amenable to resection or definitive radiotherapy) or metastatic NSCLC (with or without driver genomic alterations).
    • 12 Subjects must have previously received systemic therapy in the advanced/metastatic stage and must be intolerant/refractory to treatment or have disease progression after treatment.
    • 13 Subjects must have received one to three lines of therapy for advanced/metastatic disease and had disease progression during treatment (according to RECIST 1.1)
    • 14 If a subject received a platinum-containing regimen or targeted therapy as (neo)adjuvant treatment for early-stage disease and had relapse or metastasis during or within 3 months after completion of the regimen, this treatment can be considered as a line of treatment in the advanced-stage disease stage.
    • 15 Part A: Subjects with EGFRwt tumors with high CEACAM5 expression.
    • 16 Part B: Subjects whose tumors are known to harbor EGFR mutations and have high CEACAM5 expression according to assessment of local clinical practice.
    • 17 All other inclusion criteria defined in the protocol also needed to be met.
    • 18 Sub-study Pancreatic cancer confirmed by histology or cytology, subjects have advanced or metastatic PDAC and are intolerant/refractory to or have disease progression after systemic therapy for advanced/metastatic disease, which must include the following treatments (provided there are no medical contraindications and these drugs are approved and available locally): FOLFIRINOX or NALIRIFOX regimens (Conroy 2011; Wainberg 2023) or albumin-bound paclitaxel/gemcitabine regimens (von Hoff 2013)
    • 19 Subjects must have received one to two lines of therapy for advanced/metastatic disease and had disease progression during treatment (according to RECIST 1.1).
    • 20 All subjects were screened using IHC to determine CEACAM5 expression. Only subjects with tumors that expressed high levels of CEACAM5 were eligible to participate in this sub-study.
    • twenty one All other inclusion criteria defined in the protocol also needed to be met.
    • patients aged ≥18 years, with an Eastern Cooperative Oncology Group performance status ≤1, adequate baseline hematological, renal, and hepatic function, ≥1 lesion that is measurable using RECIST v1.1, who have received ≥1 prior line of treatment are eligible. Patients must have an archival formalin-fixed paraffin-embedded tumor tissue or a fresh biopsy. In the respective substudies, patients with advanced or metastatic, HER2 negative GC or gastroesophageal junction adenocarcinoma; patients with advanced (Stage III; ineligible for resection/curative radiation) or metastatic NSCLC; or patients with advanced or metastatic PDAC will be included. Patient selection will be based on CEACAM5 expression level (both high and low in GC, only high in NSCLC and PDAC [CEACAM5high: ≥50% tumor cells with immunohistochemistry [IHC] ≥2+ staining; CEACAM5low: <50% tumor cells with IHC ≥2+ staining]), and in patients with NSCLC, EGFR mutation status (EGFR wt and EGFR mut+).
    • Participants are capable of signing informed consent as defined in protocol.
    • Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤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.
    • 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.
    • Participants must have received and progressed (according to RECIST v1.1) 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 CEACAM5 high expressing tumors will be eligible.
    • - Substudy GC: Advanced/metastatic HER2-negative GC/GEJC
    • Substudy GC
    • • Patients with documented histopathological diagnosis of advanced/metastatic, HER2-negative, gastric or GEJ adenocarcinoma, who areintolerant/refractory to or progressed after systemic therapies (must include a fluoropyrimidine, a platinum agent, and an ICI for MSI-H/PD-LI+ With CPS 21) Must have received and progresseda on 21 and s2 treatment lines for locally advanced/metastatic disease
    • substudy NSCLC
    • Patients with histologically or cytologically documented advanced (Stage Ill not eligible for resection or curative radiation) or metastatic NSCLC with or without driver genomic alterations Must have received and progresseda on 21 and s3 treatment lines for locally advanced/metastatic disease
    • Substudy PDAC
    • • Patients with histologically or cytologically confirmed advanced/metastatic PDAC, who were intolerant/ refractory to or progressed after systemic therapies for the advanced/metastatic stage (must have included FOLFIRINOX, NALIRIFNOX, or nab-paclitaxel/gemcitabine)
    • • Must have received and progresseda on 21 and s2 treatment lines for locally advanced/metastatic disease
    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
    • 1The subject had a history of any other malignant tumor within 3 years before the enrollment date (except squamous cell carcinoma and basal cell carcinoma of the skin and carcinoma in situ of the cervix, benign prostate tumor/hyperplasia, or malignant tumors that the investigator and the sponsor's medical monitor agreed had been cured and had a very low risk of recurrence within 3 years).
    • 2Subjects with known brain metastases, except those who meet the following two criteria: All brain metastases have been treated locally and are clinically stable for at least 4 weeks prior to the first dose of study intervention. No persistent neurological symptoms related to brain disease (sequelae from brain metastasis treatment are acceptable).
    • 3Subjects with > Grade 1 diarrhea (watery stools) or intestinal obstruction.
    • 4Subjects with active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, intestinal perforation) and/or intestinal obstruction.
    • 5Cardiac arrhythmia, unstable angina, myocardial infarction, congestive heart failure (NYHA class ≥ II), or coronary revascularization within 180 days before the first dose of study intervention. Mean QTc calculated using QTcF > 470 ms.
    • 6Cerebrovascular accident/stroke occurred < 6 months before first dose of study intervention.
    • 7Other exclusion criteria defined by the protocol were met.
    • 8Non-small cell lung cancer sub-study: previously treated with irinotecan.
    • 9Gastric cancer sub-study: patients previously treated with irinotecan.
    • 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).

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Bernard Doger de Speville
    Status
    Recruitment on Hold
    Condition(s) Treated at Site
    Solid Tumor
    Gastric
    Non-Small Cell Lung Cancer
    Pancreas
    Location
    START Barcelona
    Barcelona, Spain, 08023
    Investigator
    Tatiana Hernandez Guerrero
    Status
    Recruitment on Hold
    Condition(s) Treated at Site
    Solid Tumor
    Gastric
    Non-Small Cell Lung Cancer
    Pancreas
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Maria de Miguel
    Status
    Recruitment on Hold
    Condition(s) Treated at Site
    Solid Tumor
    Gastric
    Non-Small Cell Lung Cancer
    Pancreas