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

MedImmune LLC39 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumors

Interventions

MEDI5395BIOLOGICAL

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

DurvalumabBIOLOGICAL

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 101 Years

Medical Language ↔ Plain English

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.

Locations (10)

Research Site

Phoenix, Arizona, United States

Research Site

La Jolla, California, United States

Research Site

Rochester, Minnesota, United States

Research Site

Buffalo, New York, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

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

Data from ClinicalTrials.gov

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Secondary Outcomes

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

The OR is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level and all lymph nodes (target and non-target) must be non-pathological in size (\< 10 mm in short axis). The PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.