Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MT-304 in Adults With Advanced HER2-Expressing Solid Tumors

Официальное название

A Phase 1, Open-Label, First-in-Human, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MT-304 in Adults With Advanced HER2-Expressing Solid Tumors

Обзор

This clinical trial is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of MT-304 in adults with advanced HER2-expressing solid tumors. The main questions it aims to answer are: * What is the safety profile of MT-304 when administered alone or with nivolumab? * What is the recommended Phase 2 dose (RP2D) of MT-304? Participants will: * Receive MT-304 alone (every 14 days) or with nivolumab (every 28 days). * Attend regular clinic visits for assessments and monitoring. * Continue treatment until disease progression, unacceptable toxicity, or study discontinuation.

Подробное описание

This multicenter, open-label, Phase 1 trial is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of MT-304 in adults aged 18 and older with advanced HER2-expressing solid tumors.

The study consists of two treatment modules:

* Module 1 (Monotherapy): Participants receive MT-304 every 14 days for 28-day cycles, with dosing adjustments based on clinical benefit and safety evaluations. * Module 2 (Combination Therapy): Participants receive MT-304 in combination with nivolumab, administered every 14 days and 28 days, respectively, also allowing for dosing adjustments.

The Bayesian Optimal Interval (BOIN) design will guide dose escalation, overseen by a Safety Review Committee to establish the recommended Phase 2 dose (RP2D).

Regular assessments, including vital signs and laboratory tests, will monitor safety and efficacy throughout the trial, with follow-up visits for up to 2 years post-treatment.

Вмешательства

• Препарат MT-304
  Safety, tolerability, and pharmacokinetics will be evaluated.
• Препарат MT-304 + Nivolumab
  Combination therapy begins after monotherapy dose clearance by the Safety Review Committee.

Первичные конечные точки

• Type, incidence and severity of Adverse Events [Срок оценки: Up to 90 days from the last dose of Investigational Medicinal Product (IMP)]
• Number of Participants With Change From Baseline in Vital Signs (Composite Safety Outcome) [Срок оценки: Up to 30 days from the last dose of IMP]
• Number of Participants With Abnormal Clinical Laboratory Parameters (Composite Safety Outcome) [Срок оценки: Up to 30 days from the last dose of IMP]
• Number of Participants With Change From Baseline in ECG Parameters (Composite Safety Outcome) [Срок оценки: Screening through Day 28, with assessments performed on Screening, Day 1 (pre-dose), and Day 28.]
• Maximum Tolerated Dose (MTD) [Срок оценки: 28 days from the last dose of IMP]
• Optimal Biological Dose (OBD) [Срок оценки: 28 days from the last dose of IMP]

Вторичные конечные точки (12)

• Pharmacokinetics (PK) [Срок оценки: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).]
• Pharmacokinetics (PK) [Срок оценки: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).]
• Pharmacokinetics (PK) [Срок оценки: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).]
• Pharmacokinetics (PK) [Срок оценки: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).]
• Pharmacokinetics (PK) [Срок оценки: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).]
• Pharmacokinetics (PK) [Срок оценки: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).]
• Pharmacokinetics (PK) [Срок оценки: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).]
• To assess adverse events of special interest (AESI) by measuring infusion reaction [Срок оценки: Upto 90 days from the last dose of IMP]
• To assess adverse events of special interest (AESI) by measuring cytokine release syndrome (CRS) [Срок оценки: Upto 90 days from the last dose of IMP]
• To assess adverse events of special interest (AESI) by measuring immune effector cell-associated neurotoxicity syndrome (ICANS) [Срок оценки: Upto 90 days from the last dose of IMP]
• To assess adverse events of special interest (AESI) by measuring hypersensitivity reaction [Срок оценки: Upto 90 days from the last dose of IMP]
• To assess the incidence of second primary malignancies reported as adverse events of special interest (AESI) occurring during the study treatment period and long-term follow-up. [Срок оценки: From first dose of Investigational Medicinal Product (IMP) through end of study and follow-up (up to 2 years)]

Критерии участия

Критерии включения

• Aged 18 years or above
• Histologically confirmed diagnosis of metastatic or advanced epithelial cancer expressing HER2 (Note: Participants with other tumor types expressing HER2 may be considered pending discussion with the Medical Monitor).
• Measurable lesion per RECIST 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or 1.
• Adequate Organ function

Критерии исключения

• Known active CNS metastasis and/or carcinomatous meningitis.
• Any acute illness including fever.
• History of symptomatic congestive heart failure
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Uncontrolled pleural effusion, pericardial effusion, or ascites
• Active autoimmune disease not related to prior therapy for primary malignancy that has required systemic therapy in the last 1 year.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 7 центров

• The Kinghorn Cancer Centre — Darlinghurst
• Scientia Clinical Research Ltd — Randwick
• Calvary Mater Newcastle — Waratah
• Icon Cancer Centre South Brisbane — South Brisbane
• Cancer Research SA Pty Ltd — Adelaide
• Cabrini Health — Melbourne
• Linear Clinical Research — Nedlands

Идентификаторы

NCT: NCT07334119 · MTX-HER2-304

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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