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

NCT04613492 | Terminated Phase 1 FDA Drug

• 2 other identifiers: D7880C000012020-002294-96
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 8

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.

Conditions

Solid Tumors

Keywords

Solid Tumors

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, important medical event, congenital anomaly/birth defect (in the offspring of the subject). The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  Day 1 through 76.14 weeks (maximum observed duration)

• Number of Participants With Dose-limiting Toxicities (DLTs)

  DLT: Any study drug-related Grade (G) 3 or higher toxicity; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) together with total bilirubin (TBL) ≥ 2 × ULN; Grade ≥ 2 myocarditis; Grade 2 non-infectious pneumonitis that does not resolve to ≤ G 1 within 7 days; any ≥ G 2 MEDI9253-related toxicity that prevents the administration of more than 1 dose of MEDI9253; in the sequential dosing cohorts, any ≥ Grade 2 MEDI9253-related toxicity that prevents administration of the first dose of durvalumab; any AE that after consultation with the sponsor and investigators, is deemed to be a DLT.

  From the first dose of MEDI9253 through Day 14 (single dose cohorts) or Day 28 (multiple dose cohorts)

• Number of Participants With TEAEs Leading to Discontinuation

  Participants were permanently discontinued (PED) due to TEAE if: an AE that in the opinion of the investigator or the sponsor, warrants discontinuation of further dosing; an AE that met the criteria for a DLT during the DLT-evaluation period (from the first dose of MEDI9253 through Day 14 \[single dose cohorts\] or Day 28 \[multiple dose cohorts\]) unless criteria for initiation of durvalumab are met; an AE that required permanent discontinuation of study drug per toxicity management guidelines.

  Day 1 through 76.14 weeks (maximum observed duration)

• Number of Participants With Abnormal Vital Signs Reported as TEAEs

  Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, pulse oximetry \[on MEDI9253 dosing days only\], pulse rate, and respiratory rate).

  Day 1 through 76.14 weeks (maximum observed duration)

• Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

  Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, coagulation, and urinalysis.

  Day 1 through 76.14 weeks (maximum observed duration)

• Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs

  Number of participants with abnormal ECG reported as TEAEs are reported.

  Day 1 through 76.14 weeks (maximum observed duration)

• Number of Participants With Abnormal Physical Examination Reported as TEAEs

  Number of participants with abnormal physical examination reported as TEAEs are reported.

  Day 1 through 76.14 weeks (maximum observed duration)

Secondary Outcomes (13)

• Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

  Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)

• Time to Response (TTR) According to RECIST V1.1

  Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)

• Percentage of Participants With Disease Control Rate (DCR) at 16 Weeks According to RECIST v1.1

  Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)

• Progression Free Survival (PFS) According to RECIST v1.1

  Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)

• Overall Survival (OS)

  Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)

Study Arms (6)

MEDI9253 Single Dose Level 1 + Durvalumab 1500 mg Q4W

EXPERIMENTAL

Participants will receive intravenous (IV) infusion of a single dose of MEDI9253 dose level 1 on Day 1. After 14 days (+7 days) of MEDI9253 dose, participants will receive IV durvalumab at 1500 mg once every 4 weeks (Q4W) until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years.

Biological: MEDI9253; Biological: Durvalumab

MEDI9253 Single Dose Level 2 + Durvalumab 1500 mg Q4W

EXPERIMENTAL

Participants will receive IV infusion of a single dose of MEDI9253 dose level 2 on Day 1. After 14 days (+7 days) of MEDI9253 dose, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years.

Biological: MEDI9253; Biological: Durvalumab

MEDI9253 Multiple Dose Level 2 + Durvalumab 1500 mg Q4W

EXPERIMENTAL

Participants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 2 over a maximum of 17 days, with a minimum of 5 days between each dose. After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years.

Biological: MEDI9253; Biological: Durvalumab

MEDI9253 Multiple Dose Level 3 + Durvalumab 1500 mg Q4W

EXPERIMENTAL

Participants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose. After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years.

Biological: MEDI9253; Biological: Durvalumab

MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Seq 3A-DESENS

EXPERIMENTAL

Participants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose (first dose was administered at dose level 2 while second and third doses were administered at dose level 3). After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years.

Biological: MEDI9253; Biological: Durvalumab

MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Conc3B-DESENS

EXPERIMENTAL

Participants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose (first dose was administered at dose level 2 while second and third doses were administered at dose level 3) along with IV infusion of durvalumab 1500 mg Q4W starting from Day 8 (on the same day of second dose of MEDI9253) until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years.

Biological: MEDI9253; Biological: Durvalumab

Interventions

MEDI9253 BIOLOGICAL

Participants will receive either single or multiple dose of MEDI9253; sequentially or concurrent with Durvalumab

MEDI9253 Multiple Dose Level 2 + Durvalumab 1500 mg Q4W; MEDI9253 Multiple Dose Level 3 + Durvalumab 1500 mg Q4W; MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Conc3B-DESENS; MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Seq 3A-DESENS; MEDI9253 Single Dose Level 1 + Durvalumab 1500 mg Q4W; MEDI9253 Single Dose Level 2 + Durvalumab 1500 mg Q4W

Durvalumab BIOLOGICAL

Participants will receive durvalumab treatment sequentially or concurrently with MEDI9253

MEDI9253 Multiple Dose Level 2 + Durvalumab 1500 mg Q4W; MEDI9253 Multiple Dose Level 3 + Durvalumab 1500 mg Q4W; MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Conc3B-DESENS; MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Seq 3A-DESENS; MEDI9253 Single Dose Level 1 + Durvalumab 1500 mg Q4W; MEDI9253 Single Dose Level 2 + Durvalumab 1500 mg Q4W

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be at least 18 years old at signing of informed consent.
• Body weight \> 35 kg at screening.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (8)

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Buffalo, New York, 14263, United States

Location

Research Site

New York, New York, 10032, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15232, United States

Location

Research Site

Bordeaux, 33076, France

Location

Research Site

Toulouse, 31100, France

Location

Research Site

Villejuif, 94800, France

Location

Related Links

• Redacted CSR Synopsis

MeSH Terms

Interventions

durvalumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2020
• First Posted: November 3, 2020
• Study Start: December 2, 2020
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (5); FR (3)