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

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

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Biological: MEDI9253
* Biological: Durvalumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 101 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors