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

NCT ID: NCT03889275

Last Updated: 2023-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

39 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-24

Study Completion Date

2022-12-12

Brief Summary

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

Detailed Description

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This is an Phase 1, first-in-human, open-label, dose-escalation, and dose-expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary efficacy of MEDI5395 in combination with durvalumab in participants with selected advanced solid tumors.

Conditions

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Advanced Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1A: MEDI5395 Dose Level 1 + Sequential Durvalumab

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.

Group Type EXPERIMENTAL

MEDI5395

Intervention Type BIOLOGICAL

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

Durvalumab

Intervention Type BIOLOGICAL

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

Cohort 2A: MEDI5395 Dose Level 2 + Sequential Durvalumab

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.

Group Type EXPERIMENTAL

MEDI5395

Intervention Type BIOLOGICAL

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

Durvalumab

Intervention Type BIOLOGICAL

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

Cohort 3A: MEDI5395 Dose Level 3 + Sequential Durvalumab

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.

Group Type EXPERIMENTAL

MEDI5395

Intervention Type BIOLOGICAL

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

Durvalumab

Intervention Type BIOLOGICAL

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

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

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.

Group Type EXPERIMENTAL

MEDI5395

Intervention Type BIOLOGICAL

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

Durvalumab

Intervention Type BIOLOGICAL

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

Cohort 4A: MEDI5395 Dose Level 4 + Sequential Durvalumab

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.

Group Type EXPERIMENTAL

MEDI5395

Intervention Type BIOLOGICAL

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

Durvalumab

Intervention Type BIOLOGICAL

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

Cohort 1B: MEDI5395 Dose Level 1 + Concurrent Durvalumab

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.

Group Type EXPERIMENTAL

MEDI5395

Intervention Type BIOLOGICAL

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

Durvalumab

Intervention Type BIOLOGICAL

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

Cohort 2B: MEDI5395 Dose Level 2 + Concurrent Durvalumab

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.

Group Type EXPERIMENTAL

MEDI5395

Intervention Type BIOLOGICAL

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

Durvalumab

Intervention Type BIOLOGICAL

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

Cohort 3B: MEDI5395 Dose Level 3 + Concurrent Durvalumab

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.

Group Type EXPERIMENTAL

MEDI5395

Intervention Type BIOLOGICAL

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

Durvalumab

Intervention Type BIOLOGICAL

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

Interventions

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MEDI5395

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

Intervention Type BIOLOGICAL

Durvalumab

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

Intervention Type BIOLOGICAL

Other Intervention Names

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Imfinzi

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
* Infectious disease exclusions including tuberculosis, Human immunodeficiency virus (HIV), hepatitis A, B or C, active bacterial, fungal or viral infections plus receipt of live attenuated vaccine prior to first dose of MEDI5395. (NOTE: Participants with evidence of fully recovered past hepatitis B infection who developed immunity OR hepatitis B/C with undetectable virus load and are on medications may be permitted).
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

101 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medimmune LLC

Role: STUDY_DIRECTOR

MedImmune LLC

Locations

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Research Site

Phoenix, Arizona, United States

Site Status

Research Site

La Jolla, California, United States

Site Status

Research Site

Rochester, Minnesota, United States

Site Status

Research Site

Buffalo, New York, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

Chapel Hill, North Carolina, United States

Site Status

Research Site

Pittsburgh, Pennsylvania, United States

Site Status

Research Site

Providence, Rhode Island, United States

Site Status

Research Site

Leeds, , United Kingdom

Site Status

Research Site

London, , United Kingdom

Site Status

Countries

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United States United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39551600 (View on PubMed)

Other Identifiers

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D6450C00001

Identifier Type: -

Identifier Source: org_study_id

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