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

Overview

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.

Interventions

• Drug MT-4561
  i.v.

Primary outcome measures

• Incidence of Adverse Event, Dose limiting toxicities (DLTs) [Time frame: a 28-day cycle]
• Number of Patients with Adverse events (AEs) [Time frame: Screening through 30 days after last dose]

Secondary outcome measures (12)

• Cmax of MT-4561 [Time frame: Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days)]
• time corresponding to occurrence of Cmax (tmax) [Time frame: Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days)]
• minimum observed plasma concentration (Cmin) [Time frame: Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days)]
• area under the concentration-time curve from zero up to 168 hours post-dose (AUC0-168) [Time frame: Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days)]
• Renal clearance (CL) after the first dose and at steady state [Time frame: Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days)]
• dose proportionality [Time frame: Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days)]
• accumulation ratio [Time frame: Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days)]
• Objective Response Rate (ORR) [Time frame: From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years]
• Disease control rate (DCR) [Time frame: From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years]
• Clinical benefit rate (CBR) [Time frame: From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years]
• Best overall response (BoR) [Time frame: From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years]
• Duration of Response (DoR) [Time frame: From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years]

Eligibility criteria

Main Inclusion Criteria:

Patients who have failed at least 1 prior therapy and, who have no standard treatment options demonstrated to provide clinical benefit or who are intolerable to or refuse further standard therapies will be enrolled.

• 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
• Eastern Cooperative Oncology Group (ECOG) 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 shorter, before the start of IMP administration
• QT interval corrected for heart rate using Fridericia's correction (QTcF) > 470 msec at screening

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• University of Southern California — Los Angeles
• START Midwest — Grand Rapids
• The James Cancer Hospital and Solove Research Institute at The Ohio State University Compr — Columbus
• The University of Texas MD Anderson Cancer Center — Houston

Japan · 2 centers

• National Cancer Center Hospital — Chuo-Ku
• National Cancer Center Hospital East — City

Identifiers

NCT: NCT06943521 · MT-4561-Z-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗