A Phase 1/2 Trial of TER-2013 in Patients With Solid Tumors Harboring AKT/PI3K/PTEN Pathway Alterations

Обзор

This is a Phase 1/2, open-label, multicenter study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of TER-2013 in patients with advanced solid tumors harboring AKT/PI3K/PTEN pathway alterations.

Подробное описание

This is a first-in-human clinical trial that will evaluate the safety, tolerability, and pharmacokinetics (PK) of TER-2013 as a monotherapy and in combination with fulvestrant and to determine the maximum tolerated/administered dose and preliminary clinical activity. The study consists of two parts: Part 1-Dose Escalation and Part 2 -Dose Expansion.

Вмешательства

• Препарат TER-2013
  Oral Capsules
• Препарат Fulvestrant injection
  Fulvestrant 500 mg Intramuscular Injection

Первичные конечные точки

• Number of Patients who Experience Dose-Limiting Toxicity [Срок оценки: 28 Days]
• Number of patients who experience a treatment-related adverse event [Срок оценки: Up to 2 years]
• Objective Response Rate as assessed by RECIST v1.1 [Срок оценки: Up to 2 years]
• Duration of Response as assessed by RECIST v1.1 [Срок оценки: Up to 2 years]

Вторичные конечные точки (6)

• Area under the plasma concentration-time curve for a dosing interval (AUCτ) of TER-2013 [Срок оценки: Up to 2 years]
• Maximum concentration (Cmax) of TER-2013 [Срок оценки: Up to 2 years]
• Time to maximum concentration (Tmax) of TER-2013 [Срок оценки: Up to 2 years]
• Terminal elimination half-life (T1/2) of TER-2013 [Срок оценки: Up to 2 years]
• Changes of pharmacodynamic markers of TER-2013 in tissue and/or blood as assessed by pAKT [Срок оценки: Up to 2 years]
• Changes of pharmacodynamic markers of TER-2013 in tissue and/or blood as assessed by pPRAS40 [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Metastatic or locally advanced, unresectable disease
• No available treatment with curative intent
• Presence of lesions to be evaluated per RECIST v1.1:

a. Dose Escalation: measurable or evaluable disease b. Cohort Expansion: measurable disease

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function
• Advanced solid tumor malignancy harboring an eligible AKT/PI3K/PTEN pathway alteration detected by a sponsor approved test

Key Inclusion Criteria for TER-2013 monotherapy arms:

• Histologically confirmed diagnosis of:

a. \[For TER-2013 dose escalation\]: solid tumor malignancy b. \[For TER-2013 cohort expansion\]: i. Cohort 1: ovarian cancer, cervical cancer, or squamous cell carcinoma of the head and neck, lung, or esophagus ii. Cohort 2: endometrial adenocarcinoma

• Prior therapy:

• \[For TER-2013 dose escalation\]: Received standard therapies appropriate for their tumor type and stage, unless contraindicated, intolerable, or patient refused
• \[For TER-2013 cohort expansion\]: No more than 3 prior lines of treatment in the advanced setting

Key Inclusion Criteria for TER-2013 and fulvestrant combination arms

• Histologically confirmed diagnosis of:

a. \[For TER-2013 + fulvestrant dose escalation\]: HR+/HER2- advanced unresectable or metastatic breast cancer b. \[For TER-2013 + fulvestrant cohort expansion\]: i. Received treatment with an AI containing regimen (single agent or in combination) ii. No more than 3 prior lines of treatment in the advanced unresectable or metastatic setting

• Prior Therapy:

a. \[For TER-2013 + fulvestrant dose escalation\]: Received treatment with an AI containing regimen (single agent or in combination) b. \[For TER-2013 + fulvestrant cohort expansion\]: i. Received treatment with an AI containing regimen (single agent or in combination) ii. No more than 3 prior lines of treatment in the advanced unresectable or metastatic setting

Критерии исключения

• Known EGFR, KRAS, NRAS, HRAS, or BRAF oncogenic-driver co-mutation with PI3K/AKT/PTEN alteration
• Clinically significant abnormalities of glucose metabolism
• Active brain metastases or carcinomatous meningitis.
• History of significant hemoptysis or hemorrhage within 4 weeks prior to first dose of study drug
• Malabsorption syndrome, nausea and vomiting uncontrolled by medication, or disease significantly affecting gastrointestinal function likely to interfere with the delivery, absorption, or metabolism of TER-2013
• Prior therapy:

• \[For TER-2013 monotherapy escalation\]: AKT inhibitor
• \[For TER-2013 monotherapy expansion\]: AKT/PI3K/PTEN pathway inhibitor
• \[For TER-2013 + fulvestrant combination expansion\]: AKT/PI3K/PTEN pathway inhibitor, fulvestrant and other SERDs, mTOR inhibitor; some PIK3CA-altered cohorts allow prior PI3K inhibitor.

Other protocol-defined Inclusion/Exclusion Criteria apply

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 14 центров

• Florida Cancer Specialists - Lake Nona — Orlando
• Massachusetts General Hospital — Boston
• Mayo Rochester — Rochester
• Washington Univ. School of Medicine — St Louis
• Nebraska Cancer Specialists — Omaha
• Carolina BioOncology Institute — Huntersville
• UH Cleveland Medical Center — Cleveland
• Sarah Cannon Nashville — Nashville
• … и ещё 6 центров

Пуэрто-Рико · 1 центр

• PanOncology Trials — San Juan

Идентификаторы

NCT: NCT07109726 · TER-2013-C01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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