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

Sponsor

MedImmune LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03889275

Collaborator

(none)

Enrollment

Locations

Arms

37.8

Anticipated Duration (Months)

3.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Biological: MEDI5395 Biological: Durvalumab	Phase 1

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 subjects with selected advanced solid tumors.

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Oct 24, 2019

Actual Primary Completion Date :

Nov 19, 2021

Anticipated Study Completion Date :

Dec 19, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequential MEDI5395 and durvalumab administered sequentially	Biological: MEDI5395 Subjects will receive multiple doses of MEDI5395 over several days. Biological: Durvalumab Durvalumab will be administered periodically for a maximum of 2 years or until radiologically confirmed disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity Other Names: Imfinzi
Experimental: Concurrent MEDI5395 and durvalumab administered concurrently	Biological: MEDI5395 Subjects will receive multiple doses of MEDI5395 over several days. Biological: Durvalumab Durvalumab will be administered periodically for a maximum of 2 years or until radiologically confirmed disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity Other Names: Imfinzi

Arm

Intervention/Treatment

Experimental: Sequential

MEDI5395 and durvalumab administered sequentially

Biological: MEDI5395

Subjects will receive multiple doses of MEDI5395 over several days.

Biological: Durvalumab

Durvalumab will be administered periodically for a maximum of 2 years or until radiologically confirmed disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity

Other Names:

Imfinzi

Experimental: Concurrent

MEDI5395 and durvalumab administered concurrently

Biological: MEDI5395

Subjects will receive multiple doses of MEDI5395 over several days.

Biological: Durvalumab

Durvalumab will be administered periodically for a maximum of 2 years or until radiologically confirmed disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity

Other Names:

Imfinzi

Outcome Measures

Primary Outcome Measures

Number of subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs). [From the time of informed consent until 90 days after the last dose of investigational product (MEDI5395 or durvalumab)]
The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI5395.

Secondary Outcome Measures

Objective response rate (ORR) [Estimated to be from the time of informed consent for approximately 2.5 years]
The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).
Disease Control Rate (DCR) [Estimated to be from the time of informed consent for approximately 2.5 years]
The DCR will be estimated by the proportion of disease control. Disease control is defined as CR, PR or stable disease.
Duration of Response (DoR) [Estimated to be from the time of informed consent for approximately 2.5 years]
The DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
Time To Response (TTR) [Estimated to be from the time of informed consent for approximately 2.5 years]
The TTR is defined as the time from the start of treatment with any investigational product until the first documentation of a subsequently confirmed objective response.
Progression Free Survival (PFS) [Estimated to be from the time of informed consent for approximately 2.5 years]
PFS will be measured from the start of treatment with any investigational product until the first documentation of disease progression or death due to any cause, whichever occurs first.
Overall Survival (OS) [Estimated to be from the time of informed consent for approximately 2.5 years]
OS will be measured from the start of treatment with investigational product until death due to any cause.
MEDI5395 viral genome copies in blood collected over time [Estimated to be from the time of informed consent for approximately 6 months]
MEDI5395 concentrations in blood will be tabulated by dose cohort along with descriptive statistics.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations in blood collected over time [Estimated to be from the time of informed consent for approximately 6 months]
GM-CSF protein concentrations in blood will be tabulated by dose cohort along with descriptive statistics.
Number of subjects who develop detectable anti-MEDI5395 neutralizing antibodies [Estimated to be from the time of informed consent until approximately 90 days after the last dose of last investigational product]
Immunogenic response to MEDI5395 will be assessed by summarizing the number of subjects who develop detectable anti-MEDI5395 neutralizing antibodies
Percentage of subjects who develop detectable anti-MEDI5395 neutralizing antibodies [Estimated to be from the time of informed consent until approximately 90 days after the last dose of last investigational product]
Immunogenic response to MEDI5395 will be assessed by summarizing the percentage of subjects who develop detectable anti-MEDI5395 neutralizing antibodies
The number of cluster of differentiation 8 (CD8) positive cells and programmed death-ligand 1(PD-L1) expressing cells within biopsies will be assessed. [Estimated to be from the time of informed consent until 4 weeks after the first dose of MEDI5395]
CD8 T cell infiltration and PD-L1 expression in tumors pre and post dosing will be assessed using validated IHC assays.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 101 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

The subject must consent to take precautionary measures to prevent Newcastle Disease Virus (NDV) transmission to humans and birds
Subjects 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 subjects are required to have had at least one prior line of treatment in the recurrent or metastatic setting
Subjects 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 subjects must consent to provide tumor tissue for correlative studies
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 subject that cannot tolerate a break of at least 8 weeks from systemic anticancer therapy.
Primary central nervous system (CNS) disease is excluded
Subjects 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: Subjects 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 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
Subjects 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 subject safety or study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85054
2	Research Site	La Jolla	California	United States	92093
3	Research Site	Rochester	Minnesota	United States	55905
4	Research Site	Buffalo	New York	United States	14263
5	Research Site	New York	New York	United States	10065
6	Research Site	Chapel Hill	North Carolina	United States	27599
7	Research Site	Pittsburgh	Pennsylvania	United States	15232
8	Research Site	Providence	Rhode Island	United States	02903
9	Research Site	Leeds		United Kingdom	LS9 7TF
10	Research Site	London		United Kingdom	SW3 6JJ