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

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

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.

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.