Eligible participants have histologically confirmed advanced/metastatic CRC refractory to standard therapies (MSI-H must have received checkpoint inhibitors if available), ECOG PS ≤1, and adequate organ function. Exclusions include other active malignancies (exceptions: non-melanoma skin/cervical cancers), unstable brain metastases, Grade >1 diarrhea/ileus, active IBD, significant cardiovascular events (MI/stroke within 6 months), or QTc >470 ms. Bowel obstruction/intestinal perforation history is also excluded.

This Phase 1 trial (NCT05464030) investigated the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity of M9140 as monotherapy (Q3W [Day 1 of 21-day cycles]; IV), At data cutoff (19 Jan 2024), 40 pts from the US, EU, and Japan were treated across 7 dose levels (DLs): 0.6 mg/kg, 1.2 mg/kg (n=3, each), 2.4 mg/kg (n=7), 2.6 mg/kg (n=4), 2.8 mg/ kg (n=12), 3.0 mg/kg (n 4), and 3.2 mg/kg (n=7, including 3 pts with primary G CSF prophylaxis).

This study evaluates M9140 in participants with locally advanced/metastatic colorectal cancer (CRC), divided into multiple parts. Part 1 assesses dose-limiting toxicities (DLTs) and adverse events (AEs) to determine the recommended dose expansion (RDE) over 4 months. Parts 2A, 2B, 2C, and 2D further examine safety (AEs/DLTs), objective response (OR) per RECIST v1.1, and duration of response (DoR) over 8 months.

Eligible participants have histologically confirmed advanced/metastatic CRC refractory to standard therapies (MSI-H must have received checkpoint inhibitors if available), ECOG PS ≤1, and adequate organ function. Exclusions include other active malignancies (exceptions: non-melanoma skin/cervical cancers), unstable brain metastases, Grade >1 diarrhea/ileus, active IBD, significant cardiovascular events (MI/stroke within 6 months), or QTc >470 ms. Bowel obstruction/intestinal perforation history is also excluded.

This Phase 1 trial (NCT05464030) investigated the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity of M9140 as monotherapy (Q3W [Day 1 of 21-day cycles]; IV), At data cutoff (19 Jan 2024), 40 pts from the US, EU, and Japan were treated across 7 dose levels (DLs): 0.6 mg/kg, 1.2 mg/kg (n=3, each), 2.4 mg/kg (n=7), 2.6 mg/kg (n=4), 2.8 mg/ kg (n=12), 3.0 mg/kg (n 4), and 3.2 mg/kg (n=7, including 3 pts with primary G CSF prophylaxis).

This study evaluates M9140 in participants with locally advanced/metastatic colorectal cancer (CRC), divided into multiple parts. Part 1 assesses dose-limiting toxicities (DLTs) and adverse events (AEs) to determine the recommended dose expansion (RDE) over 4 months. Parts 2A, 2B, 2C, and 2D further examine safety (AEs/DLTs), objective response (OR) per RECIST v1.1, and duration of response (DoR) over 8 months.

Eligible participants must have histologically confirmed metastatic CRC refractory to standard therapies (fluoropyrimidine, irinotecan, platinum/EGFR/VEGF inhibitors) with ECOG PS &le;1 and adequate organ function. Key exclusions include active malignancies (exceptions: non-melanoma skin/cervical cancers), unstable brain metastases, uncontrolled diarrhea/ileus (Grade >1), or recent stroke (<6 months). MSI-H participants must have received checkpoint inhibitors unless contraindicated.

Pharmacokinetic (PK) assessments will characterize plasma concentrations of M9140 across multiple cycles up to treatment discontinuation (≈20 months). Efficacy outcomes include objective response (OR), duration of response (DoR), and progression-free survival (PFS) per RECIST v1.1, measured from first treatment until disease progression/death (≈8 months).

Eligible participants must provide informed consent, have ECOG PS &le;1, adequate organ function, and &ge;1 measurable lesion per RECIST v1.1. GC substudy requires HER2-negative advanced/metastatic adenocarcinoma with 1-2 prior lines including fluoropyrimidine/platinum (and ICI for MSI-H/PD-L1+), categorized by CEACAM5 expression. NSCLC substudy enrolls stage III/IV patients with 1-3 prior lines, analyzing CEACAM5 in EGFR-mutated tumors. PDAC substudy includes 1-2 prior lines (FOLFIRINOX/nal-IRI or gem/nab-paclitaxel) with CEACAM5high expression. Key exclusions include recent malignancies (exceptions apply), unstable brain metastases, Grade >1 diarrhea/ileus, inflammatory bowel disease, significant cardiac conditions (QTc>470ms), recent stroke (<6 months), and prior irinotecan use in GC/NSCLC substudies.

Safety and efficacy outcomes for GC/NSCLC/PDAC substudies include adverse events (AEs), duration of response (DoR), disease control at Week 12, time to response, and progression-free survival (PFS) evaluated over 48 months. Pharmacokinetic analysis of M9140 plasma concentrations and anti-drug antibodies (ADA) will be monitored for approximately 12 months, with CEACAM5 expression specifically measured in the GC substudy on Day 1.