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

An Open-label, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MEDI9253, a Recombinant Newcastle Disease Virus Encoding Interleukin-12, in Combination With Durvalumab in Participants With Select Advanced/Metastatic Solid Tumors

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Biological: MEDI9253; Biological: Durvalumab

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Research Site
  • Toulouse, France, 31100
    • Research Site
  • Villejuif, France, 94800
    • Research Site
• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New York
    • Buffalo, New York, United States, 14263
      • Research Site
    • New York, New York, United States, 10032
      • Research Site
    • New York, New York, United States, 10065
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 101 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose MEDI9253, sequential Durvalumab; Various dose level cohorts for single dose MEDI9253 with sequential Durvalumab dosing	Biological: MEDI9253; Participants will receive either Single dose MEDI9253 or Multiple Dose MEDI9253; sequentially or concurrent with Durvalumab; Biological: Durvalumab; Durvalumab treatment will be started sequentially or concurrently with MEDI9253
Experimental: Multiple dose MEDI9253, sequential Durvalumab; Various dose level cohorts for multiple dose MEDI9253 with sequential Durvalumab dosing;	Biological: MEDI9253; Participants will receive either Single dose MEDI9253 or Multiple Dose MEDI9253; sequentially or concurrent with Durvalumab; Biological: Durvalumab; Durvalumab treatment will be started sequentially or concurrently with MEDI9253
Experimental: Multiple dose MEDI9253, concurrent Durvalumab; Various dose level cohorts for multiple dose MEDI9253 with concurrent Durvalumab dosing.	Biological: MEDI9253; Participants will receive either Single dose MEDI9253 or Multiple Dose MEDI9253; sequentially or concurrent with Durvalumab; Biological: Durvalumab; Durvalumab treatment will be started sequentially or concurrently with MEDI9253

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	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	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months
Duration of Response ( DoR)	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	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months
Time to Response (TTR)	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	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months
Evaluate Disease Control Rate (DCR)	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	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months
Progression Free Survival (PFS)	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	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months
Overall Survival	OS is defined as the time from first dose of treatment until documentation of death	From Day 1 through study completion, estimated to be 1 year
Number of participants with detectable viral genome copies in blood	Presence of Viremia. Viral genome copies in blood collected over time	From Day 1 through 90 days
Number of participants who have immune changes in tumor microenvironment (TME) on MEDI9253 treatment	Determine if MEDI9253 alters the TME. CD8 T cell infiltration and/or PD-L1 expression in tumors pre- and post-dosing by immunohistochemistry (IHC)	From Day 1 through 90 days
Number of participants with neutralizing antibodies to MEDI9253	Immunogenicity of MEDI9253. Markers of antiviral immune response (anti-MEDI9253 neutralizing antibodies)	From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months
IL-12 plasma concentrations	IL-12 plasma concentrations collected over time	From Day 1 through 90 days

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2020
• Primary Completion (Estimated): November 26, 2024
• Study Completion (Estimated): November 26, 2024

Study Registration Dates

• First Submitted: October 28, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): November 3, 2020

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Solid Tumors
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: D7880C00001; 2020-002294-96 (EudraCT 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.

All request 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 Pharma 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: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

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