A Study of DB-1324 in Advanced/Metastatic Gastrointestinal Tumors

Официальное название

A Phase 1/2, Multicenter, Open-Label, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1324 in Participants With Advanced/Metastatic Gastrointestinal Tumors

Обзор

This study, the first clinical trial, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of DB-1324.

Подробное описание

This is a multicenter, open-label, multiple-dose, FIH Phase 1/2 study to explore the safety, tolerability, and efficacy of DB-1324 in participants with malignant GI tumors.

The Phase 1, which includes Dose Escalation, Backfill, and Dose Expansion to identify the MTD and determine the RDEs and RP2D.

Phase 2 will confirm the safety, tolerability, and explore efficacy in selected malignant GI tumors.

For both Phase 1 and Phase 2, participants will receive study treatment until 1) disease progression, 2) loss of clinical benefit in the opinion of the investigator, 3) unacceptable toxicity, 4) withdrawal from study treatment by participant, 5) lost to follow up, or 6) another criterion for discontinuation is met, whichever occurs first.

Вмешательства

• Препарат DB-1324
  Administered I.V.

Первичные конечные точки

• Dose Escalation and Backfill parts: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. [Срок оценки: Up to safety follow-up visit, approximately 30 days post-treatment]
• Dose Escalation and Backfill parts: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. [Срок оценки: Up to safety follow-up visit, approximately 30 days post-treatment]
• Dose Escalation and Backfill parts: Percentage of participants with Treatment Emergent Adverse Events (TEAEs) , Grade ≥ 3 TEAE, TEAE leading to dose reduction/interruption/discontinuation [Срок оценки: Up to safety follow-up visit, approximately 30 days post-treatment]
• Dose Escalation and Backfill parts: Maximum Tolerated Dose(MTD) of DB-1324 [Срок оценки: Up to safety follow-up visit, approximately 30 days post-treatment]

Вторичные конечные точки (12)

• Dose Escalation and Backfill parts: Recommended Dose for Expansions(RDEs) [Срок оценки: Up to the completion of Phase 1, assessed up to 12 months]
• Dose Escalation, Backfill and Expansion parts: Recommended Phase 2 Dose(RP2D) [Срок оценки: From the beginning of first patient in (FPI) to the end of study, approximately 36 months]
• Dose Escalation and Backfill parts: Objective Response Rate (ORR) [Срок оценки: From the beginning of first patient in (FPI) to the end of study, approximately 36 months]
• Dose Escalation and Backfill parts: Duration of Response (DoR) [Срок оценки: From the beginning of first patient in (FPI) to the end of study, approximately 36 months]
• Dose Escalation and Backfill parts: Disease Control Rate (DCR) [Срок оценки: From the beginning of first patient in (FPI) to the end of study, approximately 36 months]
• Dose Escalation and Backfill parts: Time to Response (TTR) [Срок оценки: From the beginning of first patient in (FPI) to the end of study, approximately 36 months]
• Dose Escalation and Backfill parts: Progression Free Survival (PFS) [Срок оценки: From the beginning of first patient in (FPI) to the end of study, approximately 36 months]
• Dose Escalation and Backfill parts: Pharmacokinetic-AUClast [Срок оценки: Up to safety follow up visit, approx. 30 days post-treatment]
• Dose Escalation and Backfill parts: Pharmacokinetic-AUC0-τ [Срок оценки: Up to safety follow up visit, approx. 30 days post-treatment]
• Dose Escalation and Backfill parts: Pharmacokinetic-Cmax [Срок оценки: Up to safety follow up visit, approx. 30 days post-treatment]
• Dose Escalation and Backfill parts: Pharmacokinetic-Tmax [Срок оценки: Up to safety follow up visit, approx. 30 days post-treatment]
• Dose Escalation and Backfill parts: Pharmacokinetic-Cthroug [Срок оценки: Up to safety follow up visit, approx. 30 days post-treatment]

Критерии участия

Критерии включения

• Pathologically documented advanced/unresectable, or metastatic GI tumor.
• Have relapsed or progressed on or after standard systemic treatments, or are intolerant to standard treatment, or for which no standard treatment is available.
• At least one measurable lesion as assessed by the investigator according to response evaluation criteria in RECIST v1.1.
• Has a life expectancy of ≥ 3 months.
• Has an ECOG PS of 0-1.
• Has LVEF ≥ 50% by either ECHO or MUGA within 28 days before enrollment.
• Has adequate organ functions within 7 days prior to Day 1 of Cycle 1.
• Has an adequate treatment washout period before Day 1 of Cycle 1.
• Participants are willing to provide archived tumor tissue or undergo a tumor biopsy for the measurement of CDH17 levels and other biomarkers.
• Other protocol-defined Inclusion criteria apply.

Критерии исключения

• Prior treatment with CDH17 targeted therapy.
• Prior treatment with ADC with topoisomerase I inhibitor.
• Has chronic enteritis or inflammatory bowel disease. Or has clinically significant bleeding of GI tract or adjacent organs within 1 month prior to the first dose of study treatment. Or has clinically significant obstruction and/or perforation and/or fistulae (including prior GI fistula operation) of GI tract or adjacent tissues within 6 months prior to the first dose of study treatment.
• Uncontrolled or significant cardiovascular disease.
• Has a medical history of cerebrovascular accident including transient ischemic attack within 6 months before enrollment.
• Has a history of (non-infectious) ILD/pneumonitis that required steroids, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Have a lung-specific intercurrent clinically significant illness.
• Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals.
• Has clinically active brain metastases.
• Has unresolved toxicities from previous anticancer therapy.
• Other protocol-defined 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

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• USA05-0 — Port Saint Lucie
• USA02-0 — Grand Rapids
• USA01-0 — Huntersville
• USA03-0 — Cincinnati

Австралия · 3 центра

• AUS02-0 — Randwick
• AUS03-0 — South Brisbane
• AUS01-0 — Nedlands

Китай · 2 центра

• CHN01-0 — Пекин
• CHN04-0 — Пекин

Идентификаторы

NCT: NCT07263594 · DB-1324-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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