Study of D3L-002 in Subjects With Advanced Solid Tumors

Официальное название

A Phase 1, Open-label, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3L-002 (an Anti-TIGIT/Anti-PVRIG Bispecific Antibody) Monotherapy in Subjects With Advanced Solid Tumors

Обзор

This is a first-in-human, multicenter, open-label, single-arm, dose-escalation Phase 1 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of D3L-002 monotherapy in subjects with advanced solid tumors. D3L-002 will be administered as an intravenous infusion every 3 weeks (Q3W) in 21-day cycles. Approximately 24 subjects will be enrolled. Dose escalation will follow a Bayesian Optimal Interval (BOIN) design to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D).

Вмешательства

• Препарат D3L-002
  D3L-002 is an investigational anti-TIGIT/anti-PVRIG bispecific antibody administered as an intravenous infusion every 3 weeks (Q3W).

Первичные конечные точки

• Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) [Срок оценки: From first dose through 30 days after the last dose (Safety Follow-up Visit)]
• Change from Baseline in Hemoglobin [Срок оценки: From baseline through 30 days after the last dose]
• Change from Baseline in White Blood Cell Count [Срок оценки: From baseline through 30 days after the last dose]
• Change from Baseline in Platelet Count [Срок оценки: From baseline through 30 days after the last dose]
• Change from Baseline in Alanine Aminotransferase (ALT) [Срок оценки: From baseline through 30 days after the last dose]
• Change from Baseline in Aspartate Aminotransferase (AST) [Срок оценки: From baseline through 30 days after the last dose]
• Change from Baseline in Creatinine [Срок оценки: From baseline through 30 days after the last dose]
• Change from Baseline in Urine Protein [Срок оценки: From baseline through 30 days after the last dose]
• Change from Baseline in Urine Glucose [Срок оценки: From baseline through 30 days after the last dose]
• Change from Baseline in Urine Blood [Срок оценки: From baseline through 30 days after the last dose]

Вторичные конечные точки (10)

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) [Срок оценки: From Day 1 through End of Treatment (up to approximately 6 months)]
• Pharmacokinetics: Minimum (Trough) Concentration (Ctrough) [Срок оценки: From Day 1 through End of Treatment (up to approximately 6 months)]
• Pharmacokinetics: Time to Maximum Concentration (Tmax) [Срок оценки: From Day 1 through End of Treatment (up to approximately 6 months)]
• Pharmacokinetics: Terminal Half-Life (t½) [Срок оценки: From Day 1 through End of Treatment (up to approximately 6 months)]
• Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) [Срок оценки: From Day 1 through End of Treatment (up to approximately 6 months)]
• Immunogenicity: Incidence of Anti-Drug Antibodies (ADA) [Срок оценки: From baseline through Safety Follow-up Visit (up to 30 days after last dose)]
• Objective Response Rate (ORR) [Срок оценки: From first dose through disease progression or end of study (up to approximately 12 months)]
• Duration of Response (DOR) [Срок оценки: From first documented response until disease progression or death (up to approximately 12 months)]
• Disease Control Rate (DCR) [Срок оценки: From first dose through disease assessment period (up to approximately 6 months)]
• Progression-Free Survival (PFS) [Срок оценки: From first dose until disease progression or death (up to approximately 12 months)]

Критерии участия

Критерии включения

• Ability to provide written informed consent and comply with study procedures
• Age ≥18 years
• Histologically confirmed metastatic or locally advanced incurable solid tumor that has progressed after ≥1 line of therapy or has no available standard treatment
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate organ function (hematologic, hepatic, renal)
• Life expectancy ≥12 weeks
• Willingness to provide tumor tissue (if available) and blood samples
• Agreement to use effective contraception
• Negative pregnancy test for participants of childbearing potential

Критерии исключения

• Prior anti-TIGIT or anti-PVRIG therapy
• Recent anticancer therapy without adequate washout
• Active or uncontrolled illness
• Interstitial lung disease/pneumonitis
• Active Central Nervous System (CNS) disease
• Uncontrolled effusions
• Unresolved ≥Grade 2 toxicities
• Severe prior immunotherapy-related toxicity
• Active autoimmune disease
• Active infection
• Active hepatitis B/C or HIV
• Recent malignancy (exceptions apply)
• Significant cardiovascular disease
• Immunosuppressive therapy within 14 days
• Live vaccine within 30 days
• Pregnancy or breastfeeding
• Hypersensitivity to study drug
• Investigator-determined unsuitability

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07667842 · D3L-002-100

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗