A Study of MT-4561 in Patients With Various Advanced Solid Tumors

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

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.

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