A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors

Официальное название

A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1303/BNT323 in Patients With Advanced/Metastatic Solid Tumors

Обзор

This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303/BNT323 in subjects with advanced solid tumors that express HER2.

Подробное описание

This is a multicenter, non-randomized (Except for Dose Expansion 1 and Dose Expansion 9 cohorts), open-label, multiple-dose, FIH study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the MTD/RP2D; Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic HER2-expressing malignant solid tumors.

Вмешательства

• Биопрепарат DB-1303/BNT323
  Administered IV
• Препарат Pertuzumab Injection
  Administered IV
• Препарат Ritonavir
  Administered oral
• Препарат Itraconazole
  Administered oral

Первичные конечные точки

• Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. [Срок оценки: up to 21 days after C1D1]
• Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0 [Срок оценки: Up to Safety Follow-Up visit, approximately 35 days post-treatment]
• Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]
• Phase 1: Maximum Tolerated Dose (MTD) of DB-1303 [Срок оценки: Up to Safety Follow-Up visit, approximately 35 days post-treatment]
• Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303 [Срок оценки: Up to Safety Follow-Up visit, approximately 35 days post-treatment]
• Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0 [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]
• Phase 2: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]
• Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1. [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]
• Phase 2 (Dose Expansion 10 only): To evaluate the effect of ritonavir on DB-1303 and P1003 PK in subjects with HER2-expressing, HER2-amplified, or HER2-mutated advanced solid malignant tumors [Срок оценки: up to safety follow-up visit, approx. 35 days post-treatment]
• Phase 2 (Dose Expansion 10 only): To evaluate the effect of itraconazole on DB-1303 and P1003 PK in subjects with HER2-expressing, HER2-amplified, or HER2-mutated advanced solid malignant tumors. [Срок оценки: up to safety follow-up visit, approx. 35 days post-treatment]

Вторичные конечные точки (12)

• Phase 1 & Phase 2: Pharmacokinetic-AUC [Срок оценки: Up to safety follow up visit, approx. 35 days post-treatment]
• Phase 1 & Phase 2: Pharmacokinetic-Cmax [Срок оценки: Up to safety follow up visit, approx. 35 days post-treatment]
• Phase 1 & Phase 2: Pharmacokinetic-Tmax [Срок оценки: Up to safety follow up visit, approx. 35 days post-treatment]
• Phase 1 & Phase 2: Pharmacokinetic-T1/2 [Срок оценки: Up to safety follow up visit, approx. 35 days post-treatment]
• Phase 1 & Phase 2: Pharmacokinetic-Ctrough [Срок оценки: Up to safety follow up visit, approx. 35 days post-treatment]
• Phase 1 & Phase 2: Pharmacodynamics-ADA [Срок оценки: Up to safety follow up visit, approx. 35 days post-treatment]
• Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1 [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]
• Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1 [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]
• Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1 [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]
• Phase 2: Time on Therapy [Срок оценки: Up to 21 days after the participant's last dose]
• Phase 2: Percent change in target lesions as assessed by RECIST 1.1 [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]
• Phase 1 and 2 Cohort b only: Progression-Free Survival [Срок оценки: Up to follow-up period, approximately 1 year post-treatment]

Критерии участия

Критерии включения

• Has a pathologically documented HER2-positive or HER2-expressing (except for cohort 2h where the requirement is HER2-null), advanced/unresectable, recurrent, or metastatic malignant solid tumor that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
• At least 1 measurable lesion (per RECIST 1.1)
• Provide signed informed consent
• ECOG performance status (PS) of 0-1.
• LVEF ≥ 50% by ECHO or MUGA
• Adequate organ functions
• Provide pre-existing diagnosis of HER2 status or resected tumor samples or undergo fresh tumor biopsy for HER2 testing.
• Life expectancy of ≥ 3 months.

Additional Inclusion Criteria for Part 2 Expansion Group 9:

1\. Has pathologically documented advanced/unresectable, recurrent, or metastatic EC (including UCS and USPC) and has progressed on or after at least 1 line of systemic treatment including platinum-based therapy and exposure to ICI but no more than prior 3 lines of therapy for advanced/unresectable, or metastatic disease. Note: endocrine therapy will not qualify as a systemic therapy line.

Критерии исключения

• History of symptomatic CHF (New York Heart Association \[NYHA\] classes II-IV) or serious cardiac arrhythmia requiring treatment.
• History of myocardial infarction or unstable angina within 6 months before Day 1.
• Average QTcF > 450 ms in males and > 470 ms in females
• History of clinically significant lung diseases
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
• HIV infection with AIDS defining illness or active viral hepatitis.
• Clinically active brain metastases
• Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0, Grade ≤ 1 or baseline.
• A known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
• Part 2 (expansion) Only:Multiple primary malignancies within 3 years, except adequately resected non- melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 50 центров

• The first affiliated hospital of Bengbu medical college — Bengbu
• Anhui provincial hospital — Хэфэй
• The Second Hospital of Anhui Medical University — Хэфэй
• Beijing Cancer Hospital — Пекин
• Cancer Hospital Chinese Academy of Medical Science — Пекин
• The First Hospital of Jilin University — Hongcun
• Chongqing University Cancer Hospital — Чунцин
• The First affiliated Hospital of Chongqing Medical University — Чунцин
• … и ещё 42 центра

США · 35 центров

• Helios Clinical Research — Cerritos
• California Research Institute — Los Angeles
• Sharp Memorial Hospital — San Diego
• Washington Cancer Institute at MedStar Washington Hospital Center — Washington D.C.
• Advanced Research LLC — Coral Springs
• The Oncology Institute of Hope and Innovation — Lakeland
• D&H Cancer Research Center LLC — Margate
• HCA Mercy Hospital — Miami
• … и ещё 27 центров

Тайвань · 7 центров

Список центров уточняется — проверьте первичный протокол.

South Korea · 5 центров

Список центров уточняется — проверьте первичный протокол.

Австралия · 4 центра

• Scientia Clinical Research LTD — Randwick
• Macquarie Clinical Trials Unit — Sydney
• Integrated Clinical Oncology Network Pty Ltd (Icon) — South Brisbane
• Monash Health — Melbourne

Пуэрто-Рико · 1 центр

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT05150691 · DB-1303-O-1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗