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

Phase 1Not Yet RecruitingNCT07391670

AstraZeneca40 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumours

Interventions

SC durvalumab + rHuDRUG

Durvalumab + rHu will be administered subcutaneously.

IV durvalumabDRUG

Durvalumab will be administered intravenously.

TremelimumabDRUG

Tremelimumab will be administered to participants with unresectable HCC as an IV infusion.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.