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).

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.

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