An Open-label Dose Escalation/Expansion Trial to Evaluate the Safety and Anti-tumor Activity of TEV-56278 Alone or in Combination With Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors

Официальное название

A Phase 1a/1b Open-Label, Multicenter, Dose Escalation, and Dose Expansion Trial to Evaluate the Safety and Activity of TEV-56278, as a Monotherapy and in Combination With Pembrolizumab in Participants With Selected Locally Advanced or Metastatic Solid Tumors

Обзор

The primary objectives of this trial are to: * Characterize the safety and tolerability of TEV-56278 * Determine the Recommended Phase 2 Dose (RP2D) * Evaluate antitumor activity of TEV-56278 (Part 2 only) * Determine the safety and tolerability of TEV-56278 in combination with pembrolizumab * Determine a RP2D of TEV-56278 in combination with pembrolizumab The secondary objectives of this trial are to: * Characterize the serum pharmacokinetics of TEV-56278 * Evaluate the antitumor activity of TEV-56278 * Determine the safety and tolerability of TEV-56278 * Evaluate other measures of antitumor activity of TEV-56278 * Evaluate anti-tumor activity Participants will be treated up to 12 months with a follow-up period of up to 12 months after last infusion. The total duration of the trial will be up to 25 months for individual participants. Participants who exhibit a favorable benefit risk profile at the end of the 12 month trial treatment period may be offered an opportunity for an extended treatment period in which they can be treated for a maximum of 12 additional months (up to 26 additional cycles of TEV-56278).

Вмешательства

• Препарат TEV-56278
  Administered intravenously
• Препарат Pembrolizumab
  Administered intravenously

Первичные конечные точки

• Incidence of AEs with CTCAE Grade≥3 in the escalation phase [Срок оценки: Up to 15 months after 1st infusion in the escalation phase]
• Incidence of SAEs in the escalation phase [Срок оценки: Up to 15 months after 1st infusion in the escalation phase]
• Incidence of AEs meeting protocol-defined DLT criteria in the escalation phase [Срок оценки: Up to 28 days after 1st infusion in the escalation phase]
• Incidence of dose modifications due to AEs in the escalation phase [Срок оценки: Up to 12 months after 1st infusion in the escalation phase]
• Incidence of AEs leading to discontinuation in the escalation phase [Срок оценки: Up to 12 months after 1st infusion in the escalation phase]
• Recommended Phase 2 dose as monotherapy [Срок оценки: Up to 24 months after 1st infusion]
• Objective Response Rate (ORR) based on RECIST (v 1.1) criteria in the expansion phase [Срок оценки: Up to 24 months after the 1st dose in the expansion phase]
• Duration of Response (DOR) in the expansion phase [Срок оценки: Up to 24 months after the 1st dose in the expansion phase]
• Recommended Phase 2 dose in combination with Pembrolizumab [Срок оценки: Up to 24 months after 1st dose]
• Incidence of AEs with CTCAE Grade≥3 in the combination phase [Срок оценки: Up to 15 months after 1st infusion in the combination phase]

Вторичные конечные точки (11)

• AUC0-last [Срок оценки: Predose up to Day 8]
• Cmax [Срок оценки: Predose up to Day 8]
• tmax [Срок оценки: Predose up to Day 8]
• Objective Response Rate (ORR) based on RECIST (v1.1) criteria in the escalation phase [Срок оценки: Up to 24 months after 1st infusion in the escalation phase]
• Incidence of AEs with CTCAE (v5.0) Grade≥3 in the expansion phase [Срок оценки: Up to 24 months after 1st infusion in the expansion phase]
• Incidence of SAEs in the expansion phase [Срок оценки: Up to 15 months after 1st infusion in the expansion phase]
• Incidence of dose modifications due to AEs in the expansion phase [Срок оценки: Up to 12 months after 1st infusion in the expansion phase]
• Incidence of AEs leading to discontinuation in the expansion phase [Срок оценки: Up to 12 months after 1st infusion in the expansion phase]
• Disease Control Rate (DCR) according to RECIST (v1.1) criteria [Срок оценки: Up to 24 months after 1st infusion]
• Time to Respond (TTR) according to RECIST (v1.1) criteria [Срок оценки: Up to 24 months after 1st infusion]
• Objective Response Rate (ORR) based on RECIST criteria in the combination phase [Срок оценки: Up to 24 months after 1st infusion in the combination phase]

Критерии участия

Критерии включения

• Have an established histological diagnosis of selected solid tumor and must have received and progressed on established standard therapies or have been intolerant to such therapy or have been considered by the Investigator as ineligible for approved standard therapy
• Have a life expectancy≥12 weeks at the time of the screening
• Women of childbearing potential must agree to use highly effective methods of contraception for the course of the trial through 120 days after the last dose of trial medication
• Males who are sexually active with women of childbearing potential must agree to use condoms and refrain from donating sperm for the course of the trial through 120 days after the last dose of trial medication

NOTE- Additional criteria apply, please contact the investigator for more information

Критерии исключения

• Has a history of systemic treatment therapy for cancer (including chemotherapy, immunotherapy, radiotherapy, or other investigational drug) or surgery within 4 weeks prior to baseline
• Is currently receiving or has received hematopoietic colony-stimulating growth factors within 2 weeks before screening or transfusion support 4 weeks prior to screening
• Has a diagnosis of immunodeficiency
• Has active known autoimmune disease.
• Has a history of or known active brain metastases and/or carcinomatous meningitis and/or leptomeningeal metastasis
• Has active or uncontrolled serious infections requiring systemic therapy within 14 days prior to baseline
• Has a history of clinically significant cardiovascular or cerebrovascular disease in previous 6 months prior to screening
• Has evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
• Has a seizure disorder requiring therapy (such as steroids or antiepileptics)

NOTE- Additional criteria apply, please contact the investigator for more information

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

США · 11 центров

• Teva Investigational Site 12017 — Los Angeles
• Teva Investigational Site 12021 — Lake Mary
• Teva Investigational Site 12016 — Chicago
• Teva Investigational Site 12015 — Detroit
• Teva Investigational Site 12014 — Huntersville
• Teva Investigational Site 12023 — Cincinnati
• Teva Investigational Site 12058 — Pittsburgh
• Teva Investigational Site 12019 — Nashville
• … и ещё 3 центра

Канада · 1 центр

• Teva Investigational Site 11282 — Toronto

Идентификаторы

NCT: NCT06480552 · TV56278-ONC-10203 · 2026-525954-12-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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