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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04613492
• Other study ID #: D7880C00001
• Secondary ID: 2020-002294-96
• Status: Completed
• Phase: Phase 1
• Start date: December 2, 2020
• Est. completion date: May 31, 2024

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Biological:
• MEDI9253
Participants will receive either Single dose MEDI9253 or Multiple Dose MEDI9253; sequentially or concurrent with Durvalumab
• Durvalumab
Durvalumab treatment will be started sequentially or concurrently with MEDI9253

Locations

Country	Name	City	State
France	Research Site	Bordeaux
France	Research Site	Toulouse
France	Research Site	Villejuif
United States	Research Site	Buffalo	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	IL-12 plasma concentrations	IL-12 plasma concentrations collected over time	From Day 1 through 90 days