A Study of MEDI9253 in Combination With Durvalumab in Select Solid Tumors

Phase 1

Completed

• Conditions: Solid Tumors
• Interventions: Biological: MEDI9253; Biological: Durvalumab

• Registration Number: NCT04613492
• Lead Sponsor: AstraZeneca

Brief Summary

Study D7880C00001 is a first-in-human (FIH), Phase 1, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of MEDI9253 in combination with durvalumab in adult participants with select advanced/metastatic solid tumors.

Detailed Description

Up to approximately 192 participants may be assigned to study intervention in the study across approximately 30 sites globally.

Study Timeline

• Study First Submitted: 2020-10-28
• Study First Submitted QC: 2020-10-28
• Study First Posted: 2020-11-03
• Study Start: 2020-12-02
• Primary Completion: 2024-05-31
• Study Completion: 2024-05-31
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-13
• Last Update Posted: 2024-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Participant must be at least 18 years old at signing of informed consent.
2. Body weight > 35 kg at screening

Exclusion Criteria

1 Primary central nervous system (CNS) disease is excluded, as well as untreated or uncontrolled metastatic CNS involvement, leptomeningeal disease, or cord compression.

NOTE: CNS disease that has been treated and stable/controlled for at least 3 months is permitted. Participants with CNS disease controlled via systemic steroids are not permitted.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Multiple dose MEDI9253, concurrent Durvalumab	MEDI9253	Various dose level cohorts for multiple dose MEDI9253 with concurrent Durvalumab dosing.
Multiple dose MEDI9253, sequential Durvalumab	MEDI9253	Various dose level cohorts for multiple dose MEDI9253 with sequential Durvalumab dosing;
Multiple dose MEDI9253, concurrent Durvalumab	Durvalumab	Various dose level cohorts for multiple dose MEDI9253 with concurrent Durvalumab dosing.
Single dose MEDI9253, sequential Durvalumab	Durvalumab	Various dose level cohorts for single dose MEDI9253 with sequential Durvalumab dosing
Multiple dose MEDI9253, sequential Durvalumab	Durvalumab	Various dose level cohorts for multiple dose MEDI9253 with sequential Durvalumab dosing;
Single dose MEDI9253, sequential Durvalumab	MEDI9253	Various dose level cohorts for single dose MEDI9253 with sequential Durvalumab dosing

Primary Outcome Measures

Name	Time	Method
Number of participants with Dose Limiting Toxicities (DLTs) of the MEDI9253 during the dose escalation phase	Single dose cohorts: From Day 1 through 14 days Multiple dose cohorts: From Day 1 through 28 days	DLTs must be treatment related and documented as Adverse Events (AEs)
Number of participants experiencing adverse events (AEs) /serious adverse events (SAEs)	Informed consent through 90 days post last dose of study drug, estimated to be 6 months	AEs graded by NCI CTCAE v5.0
Number of participants experiencing adverse events (AEs) leading to discontinuation	Informed consent through 90-Post last dose, estimated to be 6 months	AEs graded per NCI CTCAE v5.0

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From Day 1 through study completion, estimated to be 1 year	OS is defined as the time from first dose of treatment until documentation of death
Duration of Response ( DoR)	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months	DoR is defined as duration from first documentation of confirmed objective response (OR) to the first documented progressive disease (PD) or death. Tumor assessments will be based on RECIST v1.1
Time to Response (TTR)	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months	TTR is defined as the time from the first dose of treatment until first documentation of subsequently confirmed OR. Tumor assessments will be based on RECIST v1.1
Evaluate Disease Control Rate (DCR)	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months	DCR is defined as the proportion of participants with confirmed CR or PR, or stable disease (SD). Tumor assessments will be based on RECIST v1.1
Number of participants with neutralizing antibodies to MEDI9253	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months	Immunogenicity of MEDI9253. Markers of antiviral immune response (anti-MEDI9253 neutralizing antibodies)
Overall Response Rate (ORR)	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months	ORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR). The endpoint of ORR according to RECIST v1.1, will be assessed by evaluation of the responses post baseline until progression or the start of subsequent anti-cancer therapy
Progression Free Survival (PFS)	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months	PFS is defined as the time from first dose of treatment until first documentation of PD or death. Tumor assessments will be based on RECIST v1.1
Number of participants with detectable viral genome copies in blood	From Day 1 through 90 days	Presence of Viremia. Viral genome copies in blood collected over time
Number of participants who have immune changes in tumor microenvironment (TME) on MEDI9253 treatment	From Day 1 through 90 days	Determine if MEDI9253 alters the TME. CD8 T cell infiltration and/or PD-L1 expression in tumors pre- and post-dosing by immunohistochemistry (IHC)
IL-12 plasma concentrations	From Day 1 through 90 days	IL-12 plasma concentrations collected over time

Trial Locations

Locations (1)

Research Site; 🇫🇷 Villejuif, France