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).
Description
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.
Eligibility
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.
