Clinical trial NCT03889275: A Study of MEDI5395 in Combination With Durvalumab in Participants With Select Advanced Solid Tumors
Official title: An Open-label Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MEDI5395 in Combination With Durvalumab in Subjects With Select Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: solid tumors
immunotherapy
oncolytic virus
NDV-GMCSF
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2019-03-26
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
measure: Number of Participants with Dose-limiting Toxicities (DLT)
timeFrame: Day 1 to Day 28 of first dose of MEDI5395
measure: Number of Participants with TEAEs Resulting in Permanent Discontinuation of MEDI5395
timeFrame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
measure: Number of Participants with TEAEs Resulting in Permanent Discontinuation of Durvalumab
timeFrame: From first dose of durvalumab through 14.4 months (corresponding to maximum observed duration)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
measure: Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
timeFrame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs
timeFrame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
measure: Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
timeFrame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
measure: Maximum Reduction From Baseline in Global Longitudinal Strain (GLS) Values
timeFrame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
measure: 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
timeFrame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
Secondary outcomes:
measure: Percentage of Participants with Objective Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
measure: Percentage of Participants with Disease Control (DC) per RECIST v1.1
timeFrame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
measure: Duration of Response (DoR) per RECIST v1.1
timeFrame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
measure: Time to Response (TTR) per RECIST v1.1
timeFrame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
measure: Progression-Free Survival (PFS) per RECIST v1.1
timeFrame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
measure: Overall Survival (OS)
timeFrame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
measure: Viral Genome Concentration of MEDI5395 in Whole Blood
timeFrame: Predose and end of infusion; on dose 1,2,3,4,5,6, 1 day(D) post Dose 1 and 6, 7 D post Dose 6 of MEDI5395/Cycle(C)1D15, C2D1, C3D1,C4D1, and C5D1 pre dose of durvalumab in both sequential and concurrent dosing; C1D1, C1D8, and C1D15 in sequential dosing
measure: Number of Participants With Positive Neutralizing Antibodies (nAbs) to MEDI5395
timeFrame: Day (D) of MEDI5395 (MEDI) Dose 1, 4, 6, D1 C1 and C2 of durvalumab in sequential dosing; on day of MEDI Dose 1, 4, 6; C1D15, C2D1 C3D1, C4D1 of durvalumab dose in concurrent dosing; within 28 days of last dose (LD) and 90 days post LD (14.4 months)
measure: Tumoral Cluster of Differentiation 8 Positive (CD8+) Cell Density in Tumor Tissue
timeFrame: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
measure: Percentage of Programmed Cell Death Ligand 1 (PD-L1) Positivity in Tumor Cells
timeFrame: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
measure: Percentage of PD-L1 Positvity in Whole Biopsy Sample
timeFrame: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Medimmune LLC
role: STUDY_DIRECTOR
References: