Solid Tumours
Conditions
Keywords
Pharmacokinetics, Non-small cell lung cancer (Stage III, unresectable), Small cell lung cancer (Limited stage), Hepatocellular carcinoma (Unresectable), Subcutaneous, Human hyaluronidase, Monoclonal antibody, Programmed cell death ligand 1 (PD-L1), Programmed cell death protein 1, Anticancer therapy
Brief summary
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).
Detailed 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.
Interventions
DRUGSC durvalumab + rHu
Durvalumab + rHu will be administered subcutaneously.
DRUGIV durvalumab
Durvalumab will be administered intravenously.
DRUGTremelimumab
Tremelimumab will be administered to participants with unresectable HCC as an IV infusion.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed lowest concentration before the next dose is administered (Ctrough) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the Ctrough of SC durvalumab |
| Area under the concentration-time curve | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the AUC of SC durvalumab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent volume of distribution based on the terminal phase volume (Vz[/F]) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the VZ(/F) of SC durvalumab. |
| Average drug concentration over a dosing interval (Cavg) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the Cavg of SC durvalumab. |
| Serum concentration of durvalumab | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the serum concentration of SC durvalumab at specified timepoints. |
| Number of participants with adverse events (AEs) | Up to Survival Follow-up (approximately 17 months) | To assess the safety and tolerability of SC durvalumab. |
| Number of participants with dose-limiting toxicities (DLTs) | Up to Survival Follow-up (approximately 17 months) | To assess the safety and tolerability of SC durvalumab. |
| Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the AUClast of SC durvalumab. |
| Maximum observed concentration (Cmax) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the Cmax of SC durvalumab. |
| Terminal elimination half-life (t1/2λz) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the t1/2λz of SC durvalumab. |
| Time to reach maximum concentration following drug administration (tmax) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the tmax of SC durvalumab. |
| Total body clearance/apparent total body clearance (CL[/F]) | From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months). | To characterise the CL(/F) of SC durvalumab. |
Countries
Australia, Georgia, Poland, South Korea, Taiwan
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed