Phase 1b/2 Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced NSCLC (Substudy NSCLC)

Prior treatment

• 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).
• Cerebrovascular accident/stroke (< 6 months prior to enrollment).
• Participants with prior therapy with irinotecan.

Other illness

• 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 active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease, intestinal perforation) and/or bowel obstruction.

Lab values

• 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).

Other

• Participants with diarrhea (liquid stool) or ileus Grade > 1.

• Participants are capable of signing informed consent as defined in protocol.
• Participants in Part B with CEACAM5high known EGFR mutated tumors as assessed according to local clinical practice.
• 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 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 v1.1) 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 CEACAM5high-expressing EGFR tumors (including participants with any driver genomic alterations other than EGFR mutations).