A Phase I Dose Escalation and Dose Expansion Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Durvalumab (IMFINZI-subQ)

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).

Study Overview

• Status: Recruiting
• Conditions: Solid Tumours
• Intervention / Treatment: Drug: SC durvalumab + rHu; Drug: IV durvalumab; Drug: Tremelimumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • Not yet recruiting
    • Research Site
  • St Albans, Australia, 3021
    • Not yet recruiting
    • Research Site
  • Woolloongabba, Australia, 4102
    • Not yet recruiting
    • Research Site
• Georgia
  • Batumi, Georgia, 6010
    • Recruiting
    • Research Site
  • Tbilisi, Georgia, 0114
    • Recruiting
    • Research Site
  • Tbilisi, Georgia, 0112
    • Recruiting
    • Research Site
• Poland
  • Brzozów, Poland, 36-200
    • Not yet recruiting
    • Research Site
  • Koszalin, Poland, 75-581
    • Not yet recruiting
    • Research Site
  • Lublin, Poland, 20-090
    • Not yet recruiting
    • Research Site
  • Olsztyn, Poland, 10-357
    • Not yet recruiting
    • Research Site
  • Przemyśl, Poland, 37-700
    • Recruiting
    • Research Site
• South Korea
  • Seongnam-si, South Korea, 13620
    • Recruiting
    • Research Site
  • Seoul, South Korea, 06351
    • Recruiting
    • Research Site
  • Seoul, South Korea, 5505
    • Recruiting
    • Research Site
  • Seoul, South Korea, 03722
    • Recruiting
    • Research Site
• Taiwan
  • Tainan, Taiwan, 73657
    • Not yet recruiting
    • Research Site
  • Taipei, Taiwan, 112
    • Not yet recruiting
    • Research Site
  • Taipei, Taiwan, 110
    • Recruiting
    • Research Site
  • Taoyuan, Taiwan, 333
    • Not yet recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: SC Durvalumab DL1; Participants will receive DL1 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.	Drug: SC durvalumab + rHu; Durvalumab + rHu will be administered subcutaneously.; Drug: IV durvalumab; Durvalumab will be administered intravenously.; Other Names: MEDI4736; Drug: Tremelimumab; Tremelimumab will be administered to participants with unresectable HCC as an IV infusion.
Experimental: Part 1: SC Durvalumab DL2; Participants will receive DL2 of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.	Drug: SC durvalumab + rHu; Durvalumab + rHu will be administered subcutaneously.; Drug: IV durvalumab; Durvalumab will be administered intravenously.; Other Names: MEDI4736; Drug: Tremelimumab; Tremelimumab will be administered to participants with unresectable HCC as an IV infusion.
Experimental: Part 2: Expansion Cohort, SC Durvalumab Dose Level X; Participants will receive dose level X (determined from data analysis in Part 1) of SC durvalumab + rHu followed by IV durvalumab at predefined intervals.	Drug: SC durvalumab + rHu; Durvalumab + rHu will be administered subcutaneously.; Drug: IV durvalumab; Durvalumab will be administered intravenously.; Other Names: MEDI4736; Drug: Tremelimumab; Tremelimumab will be administered to participants with unresectable HCC as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve	To characterise the AUC of SC durvalumab.	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)	To characterise the Ctrough of SC durvalumab	From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast)	To characterise the AUClast of SC durvalumab.	From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
Maximum observed concentration (Cmax)	To characterise the Cmax of SC durvalumab.	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)	To characterise the tmax of SC durvalumab.	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)	To characterise the t1/2λz of SC durvalumab.	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])	To characterise the CL(/F) of SC durvalumab.	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])	To characterise the VZ(/F) of SC durvalumab.	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)	To characterise the Cavg of SC durvalumab.	From first dose of study intervention (Day 1), at predefined intervals throughout the administration of durvalumab (approximately 17 months).
Serum concentration of durvalumab	To characterise the serum concentration of SC durvalumab at specified timepoints.	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)	To assess the safety and tolerability of SC durvalumab.	Up to Survival Follow-up (approximately 17 months)
Number of participants with dose-limiting toxicities (DLTs)	To assess the safety and tolerability of SC durvalumab.	Up to Survival Follow-up (approximately 17 months)

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Thank You Card v1.0 Master File
• Thank You Card v1.0 EN_AU
• Thank You Card v1.0 KA_GE
• Thank You Card v1.0 KO_KR
• Thank You Card v1.0 PL_PL
• Thank You Card v1.0 ZH_TW

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2026
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2027

Study Registration Dates

• First Submitted: January 30, 2026
• First Submitted That Met QC Criteria: January 30, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Pharmacokinetics; Subcutaneous; Programmed cell death protein 1; Programmed cell death ligand 1 (PD-L1); Anticancer therapy; Non-small cell lung cancer (Stage III, unresectable); Small cell lung cancer (Limited stage); Hepatocellular carcinoma (Unresectable); Human hyaluronidase
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Lung Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; durvalumab; tremelimumab
• Other Study ID Numbers: D907HC00001; 2025-521639-34-00 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No