Anti-Ly6E Exatecan ADC M7437 in Advanced Solid Tumors

Official title

A Phase 1, 2-Part, Multicenter, Open-Label, First-in-Human Study of the Anti-Ly6E Exatecan Antibody-Drug Conjugate M7437 in Participants With Advanced Solid Tumors

Overview

The purpose of this first-in-human (FIH) study is to evaluate the safety, tolerability, Pharmacokinetics (PK), and preliminary clinical activity of M7437 in participants with locally advanced or metastatic solid tumors with known Ly6E expression, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), epithelial ovarian carcinoma (EOC), squamous cell carcinoma of the head and neck (SCCHN), pancreatic ductal adenocarcinoma (PDAC), and gastric cancer (GC).

Interventions

• Drug M7437
  Participants will receive M7437 as an intravenous infusion at a dose corresponding to their assigned cohort. Dose escalation will occur between cohorts, with 3-4 participants enrolled at each dose level before proceeding to the next higher dose.
• Drug M7437
  Participants will receive M7437 at a dose that was determined as recommended dose for expansion (RDE) in Part 1.

Primary outcome measures

• Dose-escalation Cohort: Occurences of Dose Limiting Toxicities (DLTs) [Time frame: DLT period is 21 days (cycle 1)]
• Dose-escalation Cohort: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Adverse Event (AEs) [Time frame: Up to end of Part 1 of study (approximately 1 year 8 months)]

Secondary outcome measures (3)

• Dose-escalation Cohort: Plasma Concentration of M7437 [Time frame: Cycle 1 Day 1: Pre-dose, 0.25, 6, 24, 96, 168 and 336 hours post-dose; Cycle 3 Day 1: Pre-dose, 0.25, 6 and 168 hours post-dose; Pre-dose at Day 1 of Cycles 2, 4, 6, 8 until end of treatment (approximately 1 year 8 months) (Each Cycle length=21 days)]
• Dose-escalation Cohort: Overall Response (OR) According to Response Evaluation Criteria inSolid Tumor (RECIST) version 1.1 criteria as Assessed by Investigator [Time frame: From the date of first documented complete response (CR) or partial response (PR), whichever occurs first, until the first documented disease recurrence or progressive disease (PD) (assessed upto [approximately 1 year 8 months])]
• Change From The Baseline Qtc (Δqtc) At Predefined Timepoints Based on Triplicate Electrocardiogram (ECG) Measurements [Time frame: Baseline, Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 5, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 3 Day 1 (each cycle is of 21 days)]

Eligibility criteria

Inclusion criteria

• Participants have histologically proven advanced solid tumors with known prevalent and high Ly6E expression, Disease characteristic: Participants should have an unresectable locally advanced or metastatic solid tumor that is refractory to standard therapies, or have no standard therapies, or for which no standard therapy is judged appropriate by the Investigator.

For each tumor type, participants have received prior lines of therapy, where locally available:

• Non-small cell lung cancer (nonsquamous or squamous)
• Triple-negative breast cancer
• Squamous cell carcinoma of head and neck
• Pancreatic ductal adenocarcinoma
• Gastric cancer
• Epithelial ovarian cancer

• Participants with ECOG Performance Status (ECOG) less than and equal to (<=) 1
• Participants must have blood, liver, and kidney function within safe levels.
• Other protocol defined inclusion criteria may apply

Exclusion criteria

• Participant has a history of another 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/hyperplasia, 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 before the date of enrollment). History of hematopoietic allogenic transplantation.
• Participants with known brain metastases, except those meeting both of the following criteria:

• All brain metastases 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 more than (>) 1 within 1 week of Cycle1Day1.
• Participants with active chronic inflammatory bowel disease and/or bowel obstruction.
• Participants with history of serious gastrointestinal bleeding within 3 months of Cycle1Day1.
• Other protocol defined exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Other

Study locations

United States · 4 centers

• Yale University - Yale University School of Medicine — New Haven
• Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center — Huntersville
• NEXT Houston — Galveston
• NEXT Oncology - PARENT — San Antonio

Canada · 2 centers

• Princess Margaret Cancer Centre — Toronto
• BC Cancer - Vancouver - BC Cancer Agency — Vancouver

Spain · 2 centers

• Hospital Universitari Vall d'Hebron - VHIO - Oncology - Phase I Unit — Barcelona
• NEXT Madrid - Hospital Universitario Quironsalud Madrid — Madrid

Japan · 1 center

• National Cancer Center Hospital — Tokyo

Identifiers

NCT: NCT07360314 · MS743701_0001 · 176325 · 2025-523232-39-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗