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:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
Study Contact Information:
Recruitment Complete
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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.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
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
- 1The main study complies with the requirements listed in the ICF and this protocol.2ECOG fitness status ≤ 1.3Participants who meet the criteria defined in the protocol and have normal hematology, liver function, and kidney function.4Participants must have at least one lesion that can be measured using RECIST v1.1.5All other selection criteria defined in the scheme definition must also be met.6Sub-study on gastric cancer, Parts A and B: Histopathological diagnostic records show that the subject has advanced or metastatic, HER2-negative, gastric or GEJ (tumor centroid located within 2 cm proximal or distal to the GEJ) adenocarcinoma, and is intolerant/refractory to or has experienced disease progression after 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): fluoropyrimidine and platinum-based drugs. ICI (subjects with known MSI-H status or whose tumors express PD-L1 and have CPS ≥ 1).7Participants must have experienced disease progression after at least one line of treatment (according to RECIST 1.1), but no more than two lines of treatment.8Part A: Subjects with high CEACAM5 expression in GC/GEJC (defined as IHC staining intensity ≥2+ in ≥50% of tumor cells).9Part B: Subjects with low CEACAM5 expression in GC/GEJC (defined as IHC staining intensity ≥2+ in <50% of tumor cells).10All other selection criteria defined in the scheme definition must also be met.11Subsidiary study of lung cancer, Parts A and B: Subjects were histologically or cytologically confirmed to have advanced (stage III, and not suitable for resection or radical radiotherapy) or metastatic NSCLC (with or without driver genomic alterations).12Subjects must have previously received systemic therapy for advanced/metastatic stages and be intolerant/refractory to the treatment or experience disease progression after treatment.13Subjects must have received one to three lines of therapy for advanced/metastatic disease and experienced disease progression during treatment (according to RECIST 1.1).14If a subject receives a platinum-based regimen or targeted therapy as (neo)adjuvant therapy for an early stage of disease and experiences a relapse or metastasis within 3 months during or after the regimen, the treatment can be considered a line of care for an advanced stage of disease.15Part A: Subjects with tumors that highly express CEACAM5 and EGFRwt.16Part B: Evaluations conducted based on local clinical practice revealed tumor subjects known to carry EGFR mutations and high expression of CEACAM5.17All other selection criteria defined in the scheme definition must also be met.18The study included patients with histologically or cytologically confirmed advanced or metastatic pancreatic cancer (PDAC) who were intolerant/refractory to or experienced disease progression after systemic therapy for advanced/metastatic disease, which must have included the following treatments (provided there are no medical contraindications and these drugs are locally approved and available): FOLFIRINOX or NALIRIFOX regimens (Conroy 2011; Wainberg 2023) or albumin-bound paclitaxel/gemcitabine regimens (von Hoff 2013).19Subjects must have received first or second line of treatment for advanced/metastatic disease and experienced disease progression during treatment (according to RECIST 1.1).20All participants were screened using IHC assay to determine CEACAM5 expression levels. Only participants with tumors exhibiting high CEACAM5 expression were eligible to participate in this sub-study.twenty oneAll other selection criteria defined in the scheme definition must also 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).
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Status
Recruitment Complete
Condition(s) Treated at Site
Solid Tumor
Gastric
Non-Small Cell Lung Cancer
Pancreas