A Phase I Dose Escalation and Dose Expansion Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Durvalumab

Официальное название

A Phase I, Multicentre, Dose Escalation and Dose Expansion Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Durvalumab in Adult Participants With Solid Tumours

Обзор

The purpose of the study is to determine a subcutaneous (SC: under the skin) durvalumab + recombinant human hyaluronidase (rHu) dose that yields systemic drug exposure similar to intravenous (IV: into the veins) durvalumab administration and to evaluate the pharmacokinetics and safety of SC durvalumab + rHu injection in participants with different types of solid tumours (cancers).

Подробное описание

This is a Phase I, multicentre study that will consist of 2 parts -

* Part 1: Dose Escalation * Part 2: Dose Expansion

Part 1 may include participants with solid tumours - non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC) or limited-stage small cell lung cancer (LS-SCLC). It will further consist of 2 planned dose levels of SC durvalumab - Dose level 1 (DL1) and Dose level 2 (DL2).

Part 2 will include participants with unresectable HCC. It will be initiated once a dose has been identified based on Part 1.

Вмешательства

• Препарат SC durvalumab + rHu
  Durvalumab + rHu will be administered subcutaneously.
• Препарат IV durvalumab
  Durvalumab will be administered intravenously.
• Препарат Tremelimumab
  Tremelimumab will be administered to participants with unresectable HCC as an IV infusion.

Первичные конечные точки

• Area under the concentration-time curve [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Observed lowest concentration before the next dose is administered (Ctrough) [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]

Вторичные конечные точки (10)

• Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast) [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Maximum observed concentration (Cmax) [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Time to reach maximum concentration following drug administration (tmax) [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Terminal elimination half-life (t1/2λz) [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Total body clearance/apparent total body clearance (CL[/F]) [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Apparent volume of distribution based on the terminal phase volume (Vz[/F]) [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Average drug concentration over a dosing interval (Cavg) [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Serum concentration of durvalumab [Срок оценки: From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).]
• Number of participants with adverse events (AEs) [Срок оценки: Up to Survival Follow-up (approximately 17 months)]
• Number of participants with dose-limiting toxicities (DLTs) [Срок оценки: Up to Survival Follow-up (approximately 17 months)]

Критерии участия

Критерии включения

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of ≥ 12 weeks at enrolment.
• Adequate organ and marrow function.
• Minimum body weight > 30 kg.

Part 1 only:

Locally Advanced Unresectable (Stage III) NSCLC Participants -

• Histological or cytological documented evidence of NSCLC (locally advanced, unresectable, Stage III).
• Must have received at least 2 cycles of platinum-based chemotherapy concurrent with definitive radiation therapy.
• Have not progressed following definitive concurrent chemoradiation.

LS-SCLC Participants -

• Histologically or cytologically documented LS-SCLC (Stage I-III).
• Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to enrolment.
• Have not progressed following definitive concurrent chemoradiation.

Part 1 and 2:

Unresectable HCC Participants -

• Unresectable HCC based on histopathological confirmation.
• No prior systemic therapy for unresectable HCC.
• Must not be eligible for locoregional therapy for unresectable HCC.
• Child-Pugh Score class A.
• Measurable disease as defined by RECIST v1.1.

Критерии исключения

• Active or prior documented autoimmune disease requiring systemic treatment.
• Uncontrolled infection (including human immunodeficiency virus \[HIV\], hepatitis B or C).
• Prior exposure to immune checkpoint inhibitors.

Part 1 only:

Locally Advanced Unresectable (Stage III) NSCLC Participants -

• Mixed SCLC and NSCLC histology.
• Active pneumonitis or interstitial lung disease requiring systemic therapy.

LS SCLC Participants -

• Mixed SCLC and NSCLC histology.
• Extensive-stage disease.
• History of Grade ≥ 2 pneumonitis.

Part 1 and 2:

Unresectable HCC Participants -

• Hepatic encephalopathy.
• Uncontrolled ascites.
• Active gastrointestinal (GI) bleeding.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Польша · 5 центров

• Research Site — Brzozów
• Research Site — Koszalin
• Research Site — Lublin
• Research Site — Olsztyn
• Research Site — Przemyśl

South Korea · 4 центра

• Research Site — Seongnam-si
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul

Тайвань · 4 центра

• Research Site — Tainan
• Research Site — Taipei
• Research Site — Taipei
• Research Site — Taoyuan

Австралия · 3 центра

• Research Site — Fitzroy
• Research Site — St Albans
• Research Site — Woolloongabba

Грузия · 3 центра

• Research Site — Batumi
• Research Site — Tbilisi
• Research Site — Tbilisi

Идентификаторы

NCT: NCT07391670 · D907HC00001 · 2025-521639-34-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗