A Study of TRK-950 in Patients With Advanced Solid Tumors

Официальное название

A Phase I/II Study of TRK-950 in Patients With Advanced Solid Tumors

Обзор

Part 1 • To determine the safety and tolerability of TRK-950 in patients with advanced solid tumors Part 2 • To determine the safety and tolerability of TRK-950 in combination with nivolumab(NIVO) in patients with advanced solid tumors eligible for NIVO therapy Part 3 • To determine the efficacy of TRK-950 in patients with advanced/recurrent unresectable melanoma, who received prior chemotherapy with dacarbazine(DTIC) and for whom no standard therapy exists

Подробное описание

This is an open-label phase I/II study and consists of three parts. In Part 1, patients with histologically and cytologically confirmed locally advanced or metastatic solid tumors who have been refractory or intolerant to standard therapies or for whom no standard therapy exists will receive two dose level of TRK-950. In Part 2, patients with histologically and cytologically confirmed locally advanced or metastatic solid tumors who are eligible for standard therapy with NIVO 240 mg alone administered at 2-week intervals will receive two dose level of TRK-950 in combination with Nivolumab. In Part 3, patients with histologically confirmed locally advanced unresectable or metastatic melanoma (excluding uveal melanoma), who received prior chemotherapy with DTIC and for whom no standard therapy exists will receive one dose level of TRK-950. The objectives of this study are to determine the safety, tolerability, pharmacokinetic (PK) profile and the incidence of the development of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against TRK-950.

Вмешательства

• Биопрепарат TRK-950
  5 or 10 mg/kg administered intravenously over 60 minutes (weekly)
• Биопрепарат TRK-950
  10 mg/kg administered intravenously over 60 minutes (weekly)
• Биопрепарат TRK-950
  20 mg/kg administered intravenously over 60 minutes (bi-weekly)
• Препарат Nivolumab
  240 mg administered intravenously over 30 minutes (bi-weekly)
• Биопрепарат TRK-950
  10 mg/kg administered Intravenously over 60 minutes (weekly)

Первичные конечные точки

• Number of participants with dose-limiting toxicities (DLTs) (Part 1 and 2) [Срок оценки: Up to Day 28]
• Number of participants with adverse events (AEs) (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Number of participants with adverse events of special interest (AESIs) (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Number of participants with serious adverse events (SAEs) (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Objective response rate (ORR) (Part 3) [Срок оценки: Up to approximately 12 months]

Вторичные конечные точки (12)

• Area under the concentration curve (AUC) of TRK-950 (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Maximum plasma concentration (Cmax) of TRK-950 (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Time to maximum plasma concentration (Tmax) of TRK-950 (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Terminal elimination half life (t1/2) of TRK-950 (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Total body clearance (CL) of TRK-950 (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Apparent volume of distribution (Vd) of TRK-950 (Part 1 and 2) [Срок оценки: through study completion, an average of 1 year]
• Area under the concentration curve (AUC) of Nivolumab (Part 2 only) [Срок оценки: through study completion, an average of 1 year]
• Overall survival (OS) (Part 3) [Срок оценки: Up to approximately 12 months]
• Progression-free survival (PFS) (Part 3) [Срок оценки: Up to approximately 12 months]
• Best overall response (BOR) (Part 3) [Срок оценки: Up to approximately 12 months]
• Disease control rate (DCR) (Part 3) [Срок оценки: Up to approximately 12 months]
• Duration of response (DOR) (Part 3) [Срок оценки: Up to approximately 12 months]

Критерии участия

Критерии включения

• Part 1: Patients with histologically and cytologically confirmed locally advanced or metastatic solid tumors who have been refractory or intolerant to standard therapies or for whom no standard therapy exists. Part 2: Patients with histologically and cytologically confirmed locally advanced or metastatic solid tumors who are eligible for standard therapy with NIVO 240 mg alone administered at 2-week intervals.
• Part 3: Patients with histologically confirmed locally advanced unresectable or metastatic melanoma (excluding uveal melanoma), who received prior chemotherapy with DTIC and for whom no standard therapy exists
• Patients with life expectancy of at least 3 months after the start of study drug administration
• Patients aged >=18 years at the time of consent
• Patients who are able to provide written consent in person to be a subject of this study
• A negative pregnancy test before enrollment (if female of childbearing potential)

Критерии исключения

• Patients with active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy
• Pregnant women (including those who are considered possibly pregnant based on history taking, etc. by physician) or breastfeeding women (interrupting breastfeeding to enroll is also not allowed)
• Patients who are unwilling or unable to comply with the protocol specified procedures
• Patients who are positive for human immunodeficiency virus (HIV) antibody
• Patients who meet any of the following conditions on hepatitis B virus (HBV) and hepatitis C virus (HCV) testing

• Patients who are positive for hepatitis B surface antigen (HBsAg)
• Patients who are positive for HCV RNA

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Япония · 10 центров

• Nagoya City University Hospital — Nagoya
• National Hospital Organization Kyushu Cancer Center — Fukuoka
• Sapporo Medical University Hospital — Sapporo
• Kumamoto University Hospital — Kumamoto
• Shinshu University Hospital — Matsumoto
• Niigata Cancer Center Hospital — Niigata
• Saitama Medical University International Medical Center — Hidaka
• Shizuoka Cancer Center — Nagaizumi-chō
• … и ещё 2 центра

Публикации

• Koyama T, Yonemori K, Sato J, Katsuya Y, Okada M, Yoshida T, Okano F, Yamamoto N. A phase I study of TRK-950, an Anti-CAPRIN-1 antibody, as monotherapy and in combination with nivolumab in Japanese patients with advanced solid tumors. Invest New Drugs. 2026 Apr 14. doi: 10.1007/s10637-026-01609-z. Online ahead of print. PMID 41979863
• Okano F, Saito T, Minamida Y, Kobayashi S, Ido T, Miyauchi Y, Wasai U, Akazawa D, Kume M, Ishibashi M, Jiang K, Aicher A, Heeschen C, Yonehara T. Identification of Membrane-expressed CAPRIN-1 as a Novel and Universal Cancer Target, and Generation of a Therapeutic Anti-CAPRIN-1 Antibody TRK-950. Cancer Res Commun. 2023 Apr 18;3(4):640-658. doi: 10.1158/2767-9764.CRC-22-0310. eCollection 2023 Apr. PMID 37082579

Идентификаторы

NCT: NCT05423262 · 950P1V03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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