Clinical trial NCT06943521: A Study of MT-4561 in Patients With Various Advanced Solid Tumors
Official title: A Phase I/II, Dose-escalation and Dose-optimization Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of MT-4561 in Patients With Various Advanced Solid Tumors and to Evaluate Effect of MT-4561 on Pharmacokinetics of Oral Midazolam
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma (HNSCC)
Non-small Cell Lung Cancer (NSCLC)
Esophageal Cancer
Gastric Cancer
Biliary Tract Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
Breast Cancer
Ovarian Cancer
Cervical Cancer
Endometrial Cancer
Prostate Cancer
Urothelial Carcinoma
Neuroendocrine Tumor (NET)
Neuroendocrine Carcinoma (NEC)
Soft Tissue Sarcoma
NUT Carcinoma
Lead sponsor: Mitsubishi Tanabe Pharma America Inc.
Sponsor class: INDUSTRY
First posted: 2025-04-24
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a First In Human (FIH), multicenter, open-label, Phase I/II study to evaluate safety, tolerability, Pharmacokinetics (PK), pharmacodynamics, and efficacy of MT-4561 in patients with advanced solid tumors. This study will be conducted in 3 parts.

Part 1 is aimed at evaluating safety, tolerability, PK and pharmacodynamics of MT-4561 and determining the Maximum Tolerated Dose (MTD) using the Bayesian Optimal Interval (BOIN) design.

The study details and doses of Part 2 (dose-optimization) and Part 3 (Drug-Drug Interaction) will be available after review of applicable Part 1 results.


Eligibility criteria: Main Inclusion Criteria:

* Male or female patient aged 18 years or older at the time of signing the informed consent form
* ≥ 1 measurable lesion by the RECIST v1.1 and ≥ 1 disease site for tumor biopsy
* Eastern Cooperative Oncology Group performance status: 0 to 1
* Life expectancy of at least 3 months
* Adequate bone marrow function
* Adequate hepatic function
* Adequate renal function estimated creatinine clearance ≥ 60 mL/min calculated using the Cockcroft and Gault equation or by institutional method
* Part 1: Patients must have a confirmed histologic or cytologic diagnosis of one of the following solid tumors for participation in the study: head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), esophageal cancer, gastric cancer, biliary tract cancer, pancreatic ductal adenocarcinoma (PDAC), breast cancer, ovarian cancer, cervical cancer, endometrial cancer, prostate cancer, urothelial carcinoma, neuroendocrine tumor (NET) or neuroendocrine carcinoma (NEC), soft tissue sarcoma, and NUT carcinoma.

Main Exclusion Criteria:

* Patients with active brain or leptomeningeal metastases
* Any unresolved toxicity ≥ Grade 2 from previous anticancer therapy except for alopecia
* Prior systemic anticancer therapy within 4 weeks before first dose of investigational medicinal product (IMP) or 5 half-lives, whichever is shorter, and prior radiotherapy within 2 weeks before first dose of IMP
* History of congenital long QT syndrome or clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes)
* Patients who received drugs with a known risk of QT interval prolongation or Torsades de pointes within 14 days or 5 half-lives, whichever is longer, before the start of IMP administration
* QT interval corrected for heart rate using Fridericia's correction (QTcF) \> 470 msec at screening

Primary outcomes:
measure: Incidence of Adverse Event, Dose limiting toxicities (DLTs)
timeFrame: a 28-day cycle
measure: Number of Patients with Adverse events (AEs)
timeFrame: Screening through 30 days after last dose
Secondary outcomes:
measure: Cmax of MT-4561
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 22, Cycle 3 Day 1 and Day 15, Subsequent Cycle only Day 1 (each cycle is 28 days)
measure: time corresponding to occurrence of Cmax (tmax)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 22, Cycle 3 Day 1 and Day 15, Subsequent Cycle only Day 1 (each cycle is 28 days)
measure: minimum observed plasma concentration (Cmin)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 22, Cycle 3 Day 1 and Day 15, Subsequent Cycle only Day 1 (each cycle is 28 days)
measure: area under the concentration-time curve from zero up to 168 hours post-dose (AUC0-168)
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 22, Cycle 3 Day 1 and Day 15, Subsequent Cycle only Day 1 (each cycle is 28 days)
measure: clearance (CL) after the first dose and at steady state
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 22, Cycle 3 Day 1 and Day 15, Subsequent Cycle only Day 1 (each cycle is 28 days)
measure: dose proportionality
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 22, Cycle 3 Day 1 and Day 15, Subsequent Cycle only Day 1 (each cycle is 28 days)
measure: accumulation ratio
timeFrame: Cycle 1 Day 1 through Cycle 2 Day 22, Cycle 3 Day 1 and Day 15, Subsequent Cycle only Day 1 (each cycle is 28 days)
measure: Objective Response Rate (ORR)
timeFrame: From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years
measure: Progression-Free Survival (PFS)
timeFrame: From Cycle 1 Day 1 until the first documented objective disease progression or death due to any cause, whichever occurs first, up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: From Cycle 1 Day 1 until Death, up to approximately 3 years
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Mitsubishi Tanabe Pharma America Inc.
name: Head of Medical Science
role: STUDY_DIRECTOR
References: