A Study of MEDI5395 in Combination With Durvalumab in Participants With Select Advanced Solid Tumors

NCT03889275 | Completed Phase 1 FDA Drug

• 1 other identifier: D6450C00001
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 10

Brief Summary

The reason for the study is to find out if MEDI5395 and durvalumab will work and be safe for the treatment of solid tumors.

Conditions

Advanced Solid Tumors

Keywords

solid tumors; immunotherapy; oncolytic virus; NDV-GMCSF

Outcome Measures

Primary Outcomes (10)

• 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; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. 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.

  From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

• Number of Participants with Dose-limiting Toxicities (DLT)

  A DLT is defined as any toxicity not clearly and directly related to the primary disease or to another etiology and included: any Grade 3 or higher toxicity that occurs during the DLT evaluation period, aspartate aminotransferase or alanine aminotransferase \>= 3 × upper limit of normal (ULN) together with total bilirubin \>= 2 × ULN, where no other reason other than the study drugs, can be found to explain the combination of increases, Grade ≥ 2 myocarditis, Grade 2 non infectious pneumonitis that does not resolve to Grade ≤ 1 within 7 days of the initiation of maximal supportive care, any Grade \>= 2 MEDI5395 related toxicity that prevents administration of more than 1 dose of MEDI5395 within the 18-day dosing period, in sequential dosing cohorts, any Grade \>= 2 MEDI5395 related toxicity that prevents administration of the first dose of durvalumab, and any AE that, after consultation with the Sponsor and investigators, is deemed a DLT.

  Day 1 to Day 28 of first dose of MEDI5395

• Number of Participants with TEAEs Resulting in Permanent Discontinuation of MEDI5395

  Number of participants with TEAEs resulting in permanent discontinuation of MEDI5395 are reported.

  From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

• Number of Participants with TEAEs Resulting in Permanent Discontinuation of Durvalumab

  Number of participants with TEAEs resulting in permanent discontinuation of durvalumab are reported.

  From first dose of durvalumab through 14.4 months (corresponding to maximum observed duration)

• Number of Participants With Abnormal Vital Signs Reported as TEAEs

  Number of participants with abnormal vital signs (blood pressure, pulse rate, respiration rate, oxygen saturation, and body temperature) reported as TEAEs are reported.

  From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

• Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs

  Laboratory assessment included hematology, clinical chemistry, coagulation, cardiac parameters, and urinalysis. Participants with abnormal laboratory parameters reported as TEAEs are reported.

  From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

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

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

  From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

• Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

  Change from baseline in LVEF values are reported.

  From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

• Maximum Reduction From Baseline in Global Longitudinal Strain (GLS) Values

  Maximum reduction from baseline in GLS values are reported. The GLS \< 16% is abnormal, GLS \> 18% is normal, and GLS 16% to 18% is borderline.

  From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

• Number of Participants With at Least 1-Grade Shift From Baseline to Worst Post-baseline in Eastern Co-operative Oncology Group Performance Status (ECOG-PS) Score

  ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. The scores are: 0 = Fully Active, able to carry out all pre-disease performance without restrictions; 1 = Restricted activity but ambulatory and able to carry out light work or work of a sedentary nature; 2 = Ambulatory and capable of self-care but unable to carry out work activities; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely Disabled, unable to carry out any self-care and totally confined to bed or chair; 5 = Dead.

  From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

Secondary Outcomes (11)

• Percentage of Participants with Objective Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)

• Percentage of Participants with Disease Control (DC) per RECIST v1.1

  Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)

• Duration of Response (DoR) per RECIST v1.1

  Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)

• Time to Response (TTR) per RECIST v1.1

  Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)

• Progression-Free Survival (PFS) per RECIST v1.1

  Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)

Study Arms (8)

Cohort 1A: MEDI5395 Dose Level 1 + Sequential Durvalumab

EXPERIMENTAL

Participants will receive IV infusions of MEDI5395 Dose Level 1 on Days 1, 4, 8, 10, 12, and 15 followed by durvalumab every 4 weeks (Q4W) starting from 14 days after the last dose of MEDI5395 for maximum of 2 years or until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity; whichever occurs first.

Biological: MEDI5395; Biological: Durvalumab

Cohort 2A: MEDI5395 Dose Level 2 + Sequential Durvalumab

EXPERIMENTAL

Participants will receive IV infusions of MEDI5395 Dose Level 2 on Days 1, 4, 8, 10, 12, and 15 followed by durvalumab Q4W starting from 14 days after the last dose of MEDI5395 for maximum of 2 years or until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity; whichever occurs first.

Biological: MEDI5395; Biological: Durvalumab

Cohort 3A: MEDI5395 Dose Level 3 + Sequential Durvalumab

EXPERIMENTAL

Participants will receive IV infusions of MEDI5395 Dose Level 3 on Days 1, 4, 8, 10, 12, and 15 followed by durvalumab Q4W starting from 14 days after the last dose of MEDI5395 for maximum of 2 years or until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity; whichever occurs first.

Biological: MEDI5395; Biological: Durvalumab

Cohort 3A Backfill: MEDI5395 Dose Level 3 + Sequential Durvalumab

EXPERIMENTAL

Participants will receive IV infusions of MEDI5395 Dose Level 2 on Day 1 and Dose Level 3 on Days 4, 8, 10, 12, and 15 followed by durvalumab Q4W starting from 14 days after the last dose of MEDI5395 for maximum of 2 years or until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity; whichever occurs first.

Biological: MEDI5395; Biological: Durvalumab

Cohort 4A: MEDI5395 Dose Level 4 + Sequential Durvalumab

EXPERIMENTAL

Participants will receive IV infusions of MEDI5395 Dose Level 2 on Day 1 and Dose Level 4 on Days 4, 8, 10, 12, and 15 followed by durvalumab Q4W starting from 14 days after the last dose of MEDI5395 for maximum of 2 years or until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity; whichever occurs first.

Biological: MEDI5395; Biological: Durvalumab

Cohort 1B: MEDI5395 Dose Level 1 + Concurrent Durvalumab

EXPERIMENTAL

Participants will receive IV infusions of MEDI5395 Dose Level 1 on Days 1, 4, 8, 10, 12, and 15 and durvalumab Q4W, starting from the same day as third dose of MEDI5395, for maximum of 2 years or until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity; whichever occurs first.

Biological: MEDI5395; Biological: Durvalumab

Cohort 2B: MEDI5395 Dose Level 2 + Concurrent Durvalumab

EXPERIMENTAL

Participants will receive IV infusions of MEDI5395 Dose Level 2 on Days 1, 4, 8, 10, 12, and 15 and durvalumab Q4W, starting from the same day as third dose of MEDI5395, for maximum of 2 years or until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity; whichever occurs first.

Biological: MEDI5395; Biological: Durvalumab

Cohort 3B: MEDI5395 Dose Level 3 + Concurrent Durvalumab

EXPERIMENTAL

Participants will receive IV infusions of MEDI5395 Dose Level 3 on Days 1, 4, 8, 10, 12, and 15 and durvalumab Q4W, starting from the same day as third dose of MEDI5395, for maximum of 2 years or until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity; whichever occurs first.

Biological: MEDI5395; Biological: Durvalumab

Interventions

MEDI5395 BIOLOGICAL

Participants will receive multiple dose levels of MEDI5395 over several days as stated in arm description.

Cohort 1A: MEDI5395 Dose Level 1 + Sequential Durvalumab; Cohort 1B: MEDI5395 Dose Level 1 + Concurrent Durvalumab; Cohort 2A: MEDI5395 Dose Level 2 + Sequential Durvalumab; Cohort 2B: MEDI5395 Dose Level 2 + Concurrent Durvalumab; Cohort 3A Backfill: MEDI5395 Dose Level 3 + Sequential Durvalumab; Cohort 3A: MEDI5395 Dose Level 3 + Sequential Durvalumab; Cohort 3B: MEDI5395 Dose Level 3 + Concurrent Durvalumab; Cohort 4A: MEDI5395 Dose Level 4 + Sequential Durvalumab

Durvalumab BIOLOGICAL

Participants will receive IV infusion of durvalumab as stated in arm description.

Also known as: Imfinzi

Cohort 1A: MEDI5395 Dose Level 1 + Sequential Durvalumab; Cohort 1B: MEDI5395 Dose Level 1 + Concurrent Durvalumab; Cohort 2A: MEDI5395 Dose Level 2 + Sequential Durvalumab; Cohort 2B: MEDI5395 Dose Level 2 + Concurrent Durvalumab; Cohort 3A Backfill: MEDI5395 Dose Level 3 + Sequential Durvalumab; Cohort 3A: MEDI5395 Dose Level 3 + Sequential Durvalumab; Cohort 3B: MEDI5395 Dose Level 3 + Concurrent Durvalumab; Cohort 4A: MEDI5395 Dose Level 4 + Sequential Durvalumab

Eligibility Criteria

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

You may qualify if:

• The participant must consent to take precautionary measures to prevent Newcastle Disease Virus (NDV) transmission to humans and birds
• Participants must have histologic documentation of advanced solid tumor and received and have progressed, are refractory, or are intolerant to standard therapy for the specific tumor type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting
• Participants must have at least 1 measurable lesion and an additional non-lymph node non-target lesion that can be biopsied at acceptable risk as judged by the investigator. (Note: if a non-target lesion is not available or cannot be biopsied, a RECIST target, non-lymph node lesion, lesion \>= 2 cm in longest diameter may be used for non-excisional biopsy
• All participants must consent to provide tumor tissue for correlative studies
• The ECOG performance status of 0 to 1
• Adequate organ function
• Use of highly effective contraception (females) or male condom plus spermicide (males)

You may not qualify if:

• Rapidly progressing disease defined as a participant that cannot tolerate a break of at least 8 weeks from systemic anticancer therapy.
• Primary central nervous system (CNS) disease is excluded
• Participants who have received prior check point inhibitor immunotherapy within 28 days and/or oncolytic virus therapy within 90 days prior to the first dose of MEDI5395
• Unresolved toxicities from prior anticancer therapy that led to permanent discontinuation of prior immunotherapy or that required immunosuppression other than corticosteroids
• History of severe allergic reactions to any of the study drug components
• Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic test at screening
• Any conditions requiring use of any systemic immunosuppressant including systemic corticosteroids, methotrexate, azathioprine, tumor necrosis factor (TNF) inhibitor, and/or interleukin 6 (IL-6) blockers
• Active autoimmune disease or chronic inflammatory condition (Exceptions include vitiligo, alopecia, hypothyroidism on stable treatment, diverticulosis, controlled celiac disease, and chronic skin conditions not requiring systemic therapy)
• Active acquired immune-deficiency states
• Participants who are regularly exposed to poultry or birds
• Current active hepatitis or biliary disease (except for Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease)
• Clinically significant pulmonary disease and cardiac disease
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of participant safety or study results.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (10)

Research Site

Phoenix, Arizona, 85054, United States

Location

Research Site

La Jolla, California, 92093, United States

Location

Research Site

Rochester, Minnesota, 55905, United States

Location

Research Site

Buffalo, New York, 14263, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Chapel Hill, North Carolina, 27599, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15232, United States

Location

Research Site

Providence, Rhode Island, 02903, United States

Location

Research Site

Leeds, LS9 7TF, United Kingdom

Location

Research Site

London, SW3 6JJ, United Kingdom

Location

Related Publications (1)

• Davar D, Carneiro BA, Dy GK, Sheth S, Borad MJ, Harrington KJ, Patel SP, Galanis E, Samson A, Agrawal S, Chen Z, Fan C, Gong M, Burton J, Tu E, Durham N, Laubscher K, Arnaldez F, Zamarin D. Phase I study of a recombinant attenuated oncolytic virus, MEDI5395 (NDV-GM-CSF), administered systemically in combination with durvalumab in patients with advanced solid tumors. J Immunother Cancer. 2024 Nov 17;12(11):e009336. doi: 10.1136/jitc-2024-009336.

  PMID: 39551600 DERIVED

Related Links

• CSR Synopsis redacted

MeSH Terms

Interventions

durvalumab

Study Officials

• Medimmune LLC

  MedImmune LLC

  STUDY DIRECTOR

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: March 8, 2019
• First Posted: March 26, 2019
• Study Start: October 24, 2019
• Primary Completion: November 19, 2021
• Study Completion: December 12, 2022
• Last Updated: February 21, 2023

Record last verified: 2023-02

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: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

GB (2); US (8)