Description:
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.
Title
- Brief Title: A Study of MEDI9253 in Combination With Durvalumab in Select Solid Tumors
- 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 IDs
- ORG STUDY ID:
D7880C00001
- NCT ID:
NCT04613492
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| MEDI9253 | | Multiple dose MEDI9253, concurrent Durvalumab |
| Durvalumab | | Multiple dose MEDI9253, concurrent Durvalumab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Single dose MEDI9253, sequential Durvalumab | Experimental | Various dose level cohorts for single dose MEDI9253 with sequential Durvalumab dosing | |
| Multiple dose MEDI9253, sequential Durvalumab | Experimental | Various dose level cohorts for multiple dose MEDI9253 with sequential Durvalumab dosing; | |
| Multiple dose MEDI9253, concurrent Durvalumab | Experimental | Various dose level cohorts for multiple dose MEDI9253 with concurrent Durvalumab dosing. | |
Eligibility Criteria
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.
| Maximum Eligible Age: | 101 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of participants with Dose Limiting Toxicities (DLTs) of the MEDI9253 during the dose escalation phase |
| Time Frame: | Single dose cohorts: From Day 1 through 14 days Multiple dose cohorts: From Day 1 through 28 days |
| Safety Issue: | |
| Description: | DLTs must be treatment related and documented as Adverse Events (AEs) |
Secondary Outcome Measures
| Measure: | Overall Response Rate (ORR) |
| Time Frame: | From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Duration of Response ( DoR) |
| Time Frame: | From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Time to Response (TTR) |
| Time Frame: | From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Evaluate Disease Control Rate (DCR) |
| Time Frame: | From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Overall Survival |
| Time Frame: | From Day 1 through study completion, estimated to be 1 year |
| Safety Issue: | |
| Description: | OS is defined as the time from first dose of treatment until documentation of death |
| Measure: | Number of participants with detectable viral genome copies in blood |
| Time Frame: | From Day 1 through 90 days |
| Safety Issue: | |
| Description: | Presence of Viremia. Viral genome copies in blood collected over time |
| Measure: | Number of participants who have immune changes in tumor microenvironment (TME) on MEDI9253 treatment |
| Time Frame: | From Day 1 through 90 days |
| Safety Issue: | |
| Description: | Determine if MEDI9253 alters the TME. CD8 T cell infiltration and/or PD-L1 expression in tumors pre- and post-dosing by immunohistochemistry (IHC) |
| Measure: | Number of participants with neutralizing antibodies to MEDI9253 |
| Time Frame: | From Day 1 through 90 days after the last dose of study drug, estimated to be 6 months |
| Safety Issue: | |
| Description: | Immunogenicity of MEDI9253. Markers of antiviral immune response (anti-MEDI9253 neutralizing antibodies) |
| Measure: | IL-12 plasma concentrations |
| Time Frame: | From Day 1 through 90 days |
| Safety Issue: | |
| Description: | IL-12 plasma concentrations collected over time |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AstraZeneca |
Trial Keywords
Last Updated
August 4, 2021
