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MEDI5395

Phase 1

Advanced Solid Tumors | Monoclonal antibody | Oncology |AstraZeneca PLC|Last Updated: Feb 21, 2023

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDBiomarker
Total Trials1
Total Enrollment39
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03889275A Study of MEDI5395 in Combination With Durvalumab in Participants With Select Advanced Solid TumorsPHASE1 COMPLETED 39Oct 24, 2019Dec 12, 2022Feb 21, 202310 United States, United Kingdom
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Study Endpoints
Primary Endpoints
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

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.

Number of Participants with Dose-limiting Toxicities (DLT)
Day 1 to Day 28 of first dose of MEDI5395

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.

Number of Participants with TEAEs Resulting in Permanent Discontinuation of MEDI5395
From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

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

Number of Participants with TEAEs Resulting in Permanent Discontinuation of Durvalumab
From first dose of durvalumab through 14.4 months (corresponding to maximum observed duration)

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

Number of Participants With Abnormal Vital Signs Reported as TEAEs
From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

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

Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

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

Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs
From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

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

Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

Change from baseline in LVEF values are reported.

Maximum Reduction From Baseline in Global Longitudinal Strain (GLS) Values
From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)

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.

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

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.

Secondary Endpoints
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)
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Cohort 1A: MEDI5395 Dose Level 1 + Sequential DurvalumabEXPERIMENTALParticipants 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.
Cohort 2A: MEDI5395 Dose Level 2 + Sequential DurvalumabEXPERIMENTALParticipants 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.
Cohort 3A: MEDI5395 Dose Level 3 + Sequential DurvalumabEXPERIMENTALParticipants 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.
Cohort 3A Backfill: MEDI5395 Dose Level 3 + Sequential DurvalumabEXPERIMENTALParticipants 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.
Cohort 4A: MEDI5395 Dose Level 4 + Sequential DurvalumabEXPERIMENTALParticipants 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.
Cohort 1B: MEDI5395 Dose Level 1 + Concurrent DurvalumabEXPERIMENTALParticipants 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.
Cohort 2B: MEDI5395 Dose Level 2 + Concurrent DurvalumabEXPERIMENTALParticipants 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.
Cohort 3B: MEDI5395 Dose Level 3 + Concurrent DurvalumabEXPERIMENTALParticipants 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.
Interventions
NameTypeDescription
MEDI5395BIOLOGICALParticipants will receive multiple dose levels of MEDI5395 over several days as stated in arm description.
DurvalumabBIOLOGICALParticipants will receive IV infusion of durvalumab as stated in arm description.
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Eligibility Criteria
Age Range18 Years — 101 Years
SexALL
Healthy VolunteersNo
Study Sites10

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...

Countries:United StatesUnited Kingdom
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