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

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04613492

Collaborator

(none)

Enrollment

Locations

Arms

59.2

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Biological: MEDI9253 Biological: Durvalumab	Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

86 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 2, 2020

Anticipated Primary Completion Date :

Nov 7, 2025

Anticipated Study Completion Date :

Nov 7, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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
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
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
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
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)
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)
IL-12 plasma concentrations [From Day 1 through 90 days]
IL-12 plasma concentrations collected over time

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 101 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must be at least 18 years old at signing of informed consent.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	La Jolla	California	United States	92093
2	Research Site	San Francisco	California	United States	94115
3	Research Site	Santa Monica	California	United States	90404
4	Research Site	Miami	Florida	United States	33136
5	Research Site	Atlanta	Georgia	United States	30322
6	Research Site	Iowa City	Iowa	United States	52242
7	Research Site	Saint Louis	Missouri	United States	63110
8	Research Site	Buffalo	New York	United States	14263
9	Research Site	New York	New York	United States	10032
10	Research Site	New York	New York	United States	10065
11	Research Site	Chapel Hill	North Carolina	United States	27514
12	Research Site	Huntersville	North Carolina	United States	28078
13	Research Site	Pittsburgh	Pennsylvania	United States	15232
14	Research Site	Providence	Rhode Island	United States	02903
15	Research Site	Greenville	South Carolina	United States	29605
16	Research Site	Seattle	Washington	United States	98109
17	Research Site	Bordeaux		France	33076
18	Research Site	Lyon		France	69373
19	Research Site	Toulouse		France	31100
20	Research Site	Villejuif		France	94800

Sponsors and Collaborators

AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT04613492

Other Study ID Numbers:

D7880C00001

First Posted:

Nov 3, 2020

Last Update Posted:

Jul 29, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by AstraZeneca

Solid Tumors

Additional relevant MeSH terms:

Neoplasms

Durvalumab

Study Results

No Results Posted as of Jul 29, 2022