Advanced Solid TumorsPhase 1NCT03889275
A Study of MEDI5395 in Combination With Durvalumab in Participants With Select Advanced Solid Tumors
A Phase 1 study testing MEDI5395 and Durvalumab in people with Advanced Solid Tumors, run by MedImmune LLC at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 101 years
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- MEDI5395 and Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 24 Oct 2019to 12 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 101 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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).
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- 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.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States8 sites
Research Site
Buffalo, New York, 14263
Research Site
Chapel Hill, North Carolina, 27599
Research Site
La Jolla, California, 92093
Research Site
New York, New York, 10065
Research Site
Phoenix, Arizona, 85054
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
Providence, Rhode Island, 02903
Research Site
Rochester, Minnesota, 55905
United Kingdom2 sites
Research Site
Leeds, LS9 7TF
Research Site
London, SW3 6JJ
About this study
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.
The reason for the study is to find out if MEDI5395 and durvalumab will work and be safe for the treatment of solid tumors.
Read the 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.
- Conditions
- Advanced Solid Tumors
- Being tested
- MEDI5395, Durvalumab
- Keywords
- solid tumors, immunotherapy, oncolytic virus, NDV-GMCSF
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI5395Biological
Participants will receive multiple dose levels of MEDI5395 over several days as stated in arm description.
DurvalumabBiological
Also called Imfinzi
Participants will receive IV infusion of durvalumab as stated in arm description.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1A: MEDI5395 Dose Level 1 + Sequential Durvalumab | Experimental | 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. Receives: Biological: MEDI5395; Biological: Durvalumab |
| Cohort 2A: MEDI5395 Dose Level 2 + Sequential Durvalumab | Experimental | 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. Receives: Biological: MEDI5395; Biological: Durvalumab |
| Cohort 3A: MEDI5395 Dose Level 3 + Sequential Durvalumab | Experimental | 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. Receives: Biological: MEDI5395; Biological: Durvalumab |
| Cohort 3A Backfill: MEDI5395 Dose Level 3 + Sequential Durvalumab | Experimental | 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. Receives: Biological: MEDI5395; Biological: Durvalumab |
| Cohort 4A: MEDI5395 Dose Level 4 + Sequential Durvalumab | Experimental | 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. Receives: Biological: MEDI5395; Biological: Durvalumab |
| Cohort 1B: MEDI5395 Dose Level 1 + Concurrent Durvalumab | Experimental | 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. Receives: Biological: MEDI5395; Biological: Durvalumab |
| Cohort 2B: MEDI5395 Dose Level 2 + Concurrent Durvalumab | Experimental | 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. Receives: Biological: MEDI5395; Biological: Durvalumab |
| Cohort 3B: MEDI5395 Dose Level 3 + Concurrent Durvalumab | Experimental | 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. Receives: Biological: MEDI5395; Biological: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
Number of Participants with TEAEs Resulting in Permanent Discontinuation of Durvalumab
Number of participants with TEAEs resulting in permanent discontinuation of durvalumab are reported.
Measured: From first dose of durvalumab through 14.4 months (corresponding to maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Number of participants with abnormal vital signs (blood pressure, pulse rate, respiration rate, oxygen saturation, and body temperature) reported as TEAEs are reported.
Measured: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
Laboratory assessment included hematology, clinical chemistry, coagulation, cardiac parameters, and urinalysis. Participants with abnormal laboratory parameters reported as TEAEs are reported.
Measured: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs
Number of participants with abnormal ECG parameters reported as TEAEs are reported.
Measured: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
Change From Baseline in Left Ventricular Ejection Fraction (LVEF)
Change from baseline in LVEF values are reported.
Measured: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
Maximum Reduction From Baseline in Global Longitudinal Strain (GLS) Values
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.
Measured: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
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
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.
Measured: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)
Secondary outcomes (11)
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.
Measured: 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
The DC is confirmed CR, PR, or stable disease (SD) per RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions (TLs and NTLs), normalization of tumor marker level, all lymph nodes (target and non-target) must be non-pathological in size (<10 mm in short axis), and no new lesions. The PR is defined as at least a 30% decrease in sum of diameters (SoD) of TLs, taking as reference the baseline SoD and no new NTL. 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. The SD is defined as neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase of TLs to qualify for progressive disease (PD), taking as reference the smallest SoD while on study and no new lesions. The PD is defined as at least a 20% increase in SoD of TLs, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of SoD, or the appearance of new lesions.
Measured: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Duration of Response (DoR) per RECIST v1.1
DoR: Time from first documentation of OR to first documented PD or death due to any cause, whichever occurred first. OR: Confirmed CR or confirmed PR based on RECIST v1.1 guidelines. CR: Disappearance of all target and non-target lesions, normalization of tumor marker level, all lymph nodes (target and non-target) must be non-pathological in size (< 10 mm in short axis), and no new lesions. PR: At least a 30% decrease in the SoD of target lesions, taking as reference the baseline sum diameters and no new lesions. 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. PD: At least a 20% increase in SoD of target lesion, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of sum of diameters, or the appearance of new lesions. The DOR is estimated using the Kaplan-Meier method.
Measured: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Time to Response (TTR) per RECIST v1.1
The TTR is defined as the time from the start of treatment with any study drug until the first documentation of a subsequently confirmed OR. The OR is defined as confirmed CR or confirmed PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, normalization of tumor marker level, all lymph nodes (target and non-target) must be non-pathological in size (< 10 mm in short axis), and no new lesions. 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 and no new lesions. 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. The TTR is assessed using the Kaplan-Meier method.
Measured: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Progression-Free Survival (PFS) per RECIST v1.1
The PFS is defined as the time from the start of treatment with any study drug until the first documentation of disease progression or death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of sum of diameters, or the appearance of one or more new lesions. The PFS is estimated using the Kaplan-Meier method.
Measured: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Overall Survival (OS)
The OS is defined as the time from the start of treatment with study drug until death due to any cause. The OS is estimated using the Kaplan-Meier method.
Measured: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Viral Genome Concentration of MEDI5395 in Whole Blood
Viral genome concentration of MEDI5395 in whole blood is reported.
Measured: 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
Number of Participants With Positive Neutralizing Antibodies (nAbs) to MEDI5395
Number of participants with positive nAbs to MEDI5395 are reported. Persistent positive is defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive assessment) or positive at last post-baseline assessment. Transient positive is defined as negative at the last post-baseline assessment and positive at only 1 post-baseline assessment or at >= 2 post-baseline assessments (with < 16 weeks between the first and last positive assessment).
Measured: 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)
Tumoral Cluster of Differentiation 8 Positive (CD8+) Cell Density in Tumor Tissue
The CD8+ cells were assessed by validated immunohistochemical (IHC) assays using tumor tissue from an archival or newly obtained biopsy. The results of CD8+ cell density was reported as number of CD8+ positive cells per mm^2.
Measured: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
Percentage of Programmed Cell Death Ligand 1 (PD-L1) Positivity in Tumor Cells
The PD-L1 expression was assessed by validated IHC assays using tumor tissue from an archival or newly obtained biopsy. Tumor cells were analyzed for PD-L1 expression to determine the tumor cells positivity for PD-L1.
Measured: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
Percentage of PD-L1 Positvity in Whole Biopsy Sample
The PD-L1 expression was assessed by validated IHC assays using tumor tissue from an archival or newly obtained biopsy. The whole biopsy sample (without differentiation between tumor or stromal/immune compartments) was analyzed for PD-L1 expression to determine total tissue positivity (TIP) for PD-L1.
Measured: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2019
- Study start24 Oct 2019
- Primary completion19 Nov 2021
- Study completion12 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medimmune LLC, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03889275
- Sponsor's protocol ID
- D6450C00001
- Status last verified
- Feb 2023
- First submitted
- 8 Mar 2019
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Publications
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.
PubMed 39551600
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03889275
- Acronym / sponsor ID
- D6450C00001
- Conditions
- Advanced Solid Tumors
- Keywords
- solid tumors, immunotherapy, oncolytic virus, NDV-GMCSF
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2019 (actual)
- Primary completion
- 19 Nov 2021 (actual)
- Study completion
- 12 Dec 2022 (actual)
- First posted
- 26 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Cohort 1A: MEDI5395 Dose Level 1 + Sequential Durvalumab | Experimental | Biological: MEDI5395, Biological: DurvalumabParticipants 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 Durvalumab | Experimental | Biological: MEDI5395, Biological: DurvalumabParticipants 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 Durvalumab | Experimental | Biological: MEDI5395, Biological: DurvalumabParticipants 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 Durvalumab | Experimental | Biological: MEDI5395, Biological: DurvalumabParticipants 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 Durvalumab | Experimental | Biological: MEDI5395, Biological: DurvalumabParticipants 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 Durvalumab | Experimental | Biological: MEDI5395, Biological: DurvalumabParticipants 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 Durvalumab | Experimental | Biological: MEDI5395, Biological: DurvalumabParticipants 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 Durvalumab | Experimental | Biological: MEDI5395, Biological: DurvalumabParticipants 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. |
Who may qualify
- Ages
- 18 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI5395Participants will receive multiple dose levels of MEDI5395 over several days as stated in arm description. | Biological | Cohort 1A: MEDI5395 Dose Level 1 + Sequential Durvalumab, Cohort 1B: MEDI5395 Dose Level 1 + Concurrent Durvalumab, Cohort 2A: MEDI5395 Dose Level 2 + Sequential Durvalumab, Cohort 2B: MEDI5395 Dose Level 2 + Concurrent Durvalumab, Cohort 3A Backfill: MEDI5395 Dose Level 3 + Sequential Durvalumab, Cohort 3A: MEDI5395 Dose Level 3 + Sequential Durvalumab, Cohort 3B: MEDI5395 Dose Level 3 + Concurrent Durvalumab, Cohort 4A: MEDI5395 Dose Level 4 + Sequential Durvalumab |
| DurvalumabAlso: ImfinziParticipants will receive IV infusion of durvalumab as stated in arm description. | Biological | Cohort 1A: MEDI5395 Dose Level 1 + Sequential Durvalumab, Cohort 1B: MEDI5395 Dose Level 1 + Concurrent Durvalumab, Cohort 2A: MEDI5395 Dose Level 2 + Sequential Durvalumab, Cohort 2B: MEDI5395 Dose Level 2 + Concurrent Durvalumab, Cohort 3A Backfill: MEDI5395 Dose Level 3 + Sequential Durvalumab, Cohort 3A: MEDI5395 Dose Level 3 + Sequential Durvalumab, Cohort 3B: MEDI5395 Dose Level 3 + Concurrent Durvalumab, Cohort 4A: MEDI5395 Dose Level 4 + Sequential Durvalumab |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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.
11 secondary outcomes
Percentage of Participants with Objective Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: 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
Time frame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Duration of Response (DoR) per RECIST v1.1
Time frame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Time to Response (TTR) per RECIST v1.1
Time frame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Progression-Free Survival (PFS) per RECIST v1.1
Time frame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Overall Survival (OS)
Time frame: Baseline (Day -28 to Day -1) through 24.5 months (corresponding to maximum observed duration)
Viral Genome Concentration of MEDI5395 in Whole Blood
Time frame: 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
Number of Participants With Positive Neutralizing Antibodies (nAbs) to MEDI5395
Time frame: 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)
Tumoral Cluster of Differentiation 8 Positive (CD8+) Cell Density in Tumor Tissue
Time frame: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
Percentage of Programmed Cell Death Ligand 1 (PD-L1) Positivity in Tumor Cells
Time frame: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
Percentage of PD-L1 Positvity in Whole Biopsy Sample
Time frame: Baseline (Pre-treatment) and on the Day of Dose 4 of MEDI5395 (Post-treatment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Derived from this study: PubMed 39551600Davar 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.
- CSR Synopsis redactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medimmune LLC study director
MedImmune LLC
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MEDI5395 and Durvalumab in people with Advanced Solid Tumors, run by MedImmune LLC at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) (time frame: From first dose of MEDI5395 through 14.4 months (corresponding to maximum observed duration)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03889275, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.