Biliary Tract Cancer, Breast Cancer, Cervical Cancer, Endometrial Cancer, Esophageal Cancer, Gastric Cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), Neuroendocrine Carcinoma (NEC), Neuroendocrine Tumor (NET), Non-small Cell Lung Cancer (NSCLC), Nuclear Protein in Testis (NUT) Carcinoma, Ovarian Cancer, Pancreatic Ductal Adenocarcinoma (PDAC), Prostate Cancer, Soft Tissue Sarcoma, Urothelial Carcinoma
Conditions
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.
Interventions
DRUGMT-4561
i.v.
Sponsors
Tanabe Pharma America, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Event, Dose limiting toxicities (DLTs) | a 28-day cycle | Part 1 Frequency, duration, and severity (Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) of adverse events, dose limiting toxicity (DLT), physical examinations, changes in clinical laboratory values (e.g., hematology, chemistry, and urinalysis), vital signs (e.g., heart rate, blood pressure, respiratory rate), electrocardiogram DLTs are defined as any event meeting the DLT criteria at least possibly related to MT-4561 for Cycle 1 (i.e., DLT monitoring window is approximately 28 days). Events with a clear alternative explanation will not be considered DLTs. |
| Number of Patients with Adverse events (AEs) | Screening through 30 days after last dose | Part 1 Frequency, duration, and severity (Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) of adverse events, dose limiting toxicity (DLT), physical examinations, changes in clinical laboratory values (e.g., hematology, chemistry, and urinalysis), vital signs (e.g., heart rate, blood pressure, respiratory rate), electrocardiogram Adverse event: An AE is defined as any untoward medical occurrence in a clinical study patient administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of an IMP, whether it is considered related to the IMP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| minimum observed plasma concentration (Cmin) | Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days) | To determine the pharmacokinetics(PK) profile of MT-4561 |
| area under the concentration-time curve from zero up to 168 hours post-dose (AUC0-168) | Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days) | To determine the pharmacokinetics(PK) profile of MT-4561 |
| Renal clearance (CL) after the first dose and at steady state | Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days) | To determine the pharmacokinetics(PK) profile of MT-4561 |
| dose proportionality | Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days) | To determine the pharmacokinetics(PK) profile of MT-4561 |
| accumulation ratio | Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days) | To determine the pharmacokinetics(PK) profile of MT-4561 |
| Objective Response Rate (ORR) | From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years | ORR defined as the proportion of patients with a best overall response of complete response (CR) and partial response (PR) recorded from start of study intervention until the last objective response documented. |
| Cmax of MT-4561 | Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days) | To determine the pharmacokinetics(PK) profile of MT-4561 |
| Clinical benefit rate (CBR) | From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years | CBR defined as the proportion of patients with best overall response of complete response (CR), partial response (PR), or who have had stable disease (SD) for a minimum of 6 months after the first dose of study intervention. |
| Best overall response (BoR) | From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years | BoR defined as the best response in the order of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) among all overall responses recorded from the start of the study intervention until the last objective response recorded. |
| Duration of Response (DoR) | From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years | Investigator Review according to RECIST v1.1 criteria |
| Progression-Free Survival (PFS) | 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 | Investigator Review according to RECIST v1.1 criteria |
| Overall Survival (OS) | From Cycle 1 Day 1 until Death, up to approximately 3 years | Investigator Review according to RECIST v1.1 criteria |
| Duration of stable disease (SD) | From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years | Time from the date of the first dose of the study intervention to the first documented progressive disease (PD). |
| Disease control rate (DCR) | From Cycle 1 Day 1 until Progressive Disease/Death/or start of new anticancer therapy, up to approximately 3 years | DCR defined as the proportion of patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD). |
| time corresponding to occurrence of Cmax (tmax) | Cycle 1 Day 1 through Cycle 2 Day 22 (each cycle is 28 days) | To determine the pharmacokinetics(PK) profile of MT-4561 |
Countries
Japan, United States
Contacts
Primary ContactClinical Trials Information Desk, to prevent miscommunication,
Outcome results
None listed