Anti-Ly6E Exatecan ADC M7437 in Advanced Solid Tumors
ConditionAdvanced Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorEMD Serono Research & Development Institute, Inc.
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Non-small cell lung cancer (nonsquamous or squamous)
Triple-negative breast cancer
Squamous cell carcinoma of head and neck
Disqualifiers
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.
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.
Trial design
Design model
Sequential
Treatments tested in this trial
M7437
DrugParticipants 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.
M7437
DrugParticipants will receive M7437 at a dose that was determined as recommended dose for expansion (RDE) in Part 1.
Treatment groups
138 Participants
are divided into 2 treatment groupsGroup A: Part 1: Dose-escalation CohortExperimental treatment 1 intervention
Group B: Part 2: Dose-Expansion CohortExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Dose-escalation Cohort: Occurences of Dose Limiting Toxicities (DLTs)
Time frame
DLT period is 21 days (cycle 1)2
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 outcomes
1
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)2
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])3
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)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
EMD Serono Research & Development Institute, Inc.
Lead sponsor
Merck KGaA, Darmstadt, Germany
Collaborator
Source ClinicalTrials.gov