Solid TumorsPhase 1NCT04613492
A Study of MEDI9253 in Combination With Durvalumab in Select Solid Tumors
A Phase 1 study testing MEDI9253 and Durvalumab in people with Solid Tumors, run by AstraZeneca at 8 sites in 2 countries.
Trial summary
Study D7880C00001 is a first-in-human (FIH), Phase 1, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of MEDI9253 in combination with durvalumab in adult participants with select advanced/metastatic solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 101 years
- Conditions the study is for
- Solid Tumors
- What is being tested?
- MEDI9253 and Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 2 Dec 2020to 31 May 2024
- 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
- Participant must be at least 18 years old at signing of informed consent.
- Body weight > 35 kg at screening.
Who cannot join
- 1 Primary central nervous system (CNS) disease is excluded, as well as untreated or uncontrolled metastatic CNS involvement, leptomeningeal disease, or cord compression.
- NOTE: CNS disease that has been treated and stable/controlled for at least 3 months is permitted. Participants with CNS disease controlled via systemic steroids are not permitted.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States5 sites
Research Site
Buffalo, New York, 14263
Research Site
New York, New York, 10032
Research Site
New York, New York, 10065
Research Site
Pittsburgh, Pennsylvania, 15232
Research Site
St Louis, Missouri, 63110
France3 sites
Research Site
Bordeaux, 33076
Research Site
Toulouse, 31100
Research Site
Villejuif, 94800
About this study
Official title: An Open-label, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MEDI9253, a Recombinant Newcastle Disease Virus Encoding Interleukin-12, in Combination With Durvalumab in Participants With Select Advanced/Metastatic Solid Tumors
Study D7880C00001 is a first-in-human (FIH), Phase 1, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of MEDI9253 in combination with durvalumab in adult participants with select advanced/metastatic solid tumors.
Read the detailed description
Up to approximately 192 participants may be assigned to study intervention in the study across approximately 30 sites globally.
- Conditions
- Solid Tumors
- Being tested
- MEDI9253, Durvalumab
- Keywords
- Solid Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI9253Biological
Participants will receive either single or multiple dose of MEDI9253; sequentially or concurrent with Durvalumab
DurvalumabBiological
Participants will receive durvalumab treatment sequentially or concurrently with MEDI9253
| Study group | Role | What they receive |
|---|---|---|
| MEDI9253 Single Dose Level 1 + Durvalumab 1500 mg Q4W | Experimental | Participants will receive intravenous (IV) infusion of a single dose of MEDI9253 dose level 1 on Day 1. After 14 days (+7 days) of MEDI9253 dose, participants will receive IV durvalumab at 1500 mg once every 4 weeks (Q4W) until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. Receives: Biological: MEDI9253; Biological: Durvalumab |
| MEDI9253 Single Dose Level 2 + Durvalumab 1500 mg Q4W | Experimental | Participants will receive IV infusion of a single dose of MEDI9253 dose level 2 on Day 1. After 14 days (+7 days) of MEDI9253 dose, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. Receives: Biological: MEDI9253; Biological: Durvalumab |
| MEDI9253 Multiple Dose Level 2 + Durvalumab 1500 mg Q4W | Experimental | Participants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 2 over a maximum of 17 days, with a minimum of 5 days between each dose. After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. Receives: Biological: MEDI9253; Biological: Durvalumab |
| MEDI9253 Multiple Dose Level 3 + Durvalumab 1500 mg Q4W | Experimental | Participants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose. After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. Receives: Biological: MEDI9253; Biological: Durvalumab |
| MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Seq 3A-DESENS | Experimental | Participants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose (first dose was administered at dose level 2 while second and third doses were administered at dose level 3). After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. Receives: Biological: MEDI9253; Biological: Durvalumab |
| MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Conc3B-DESENS | Experimental | Participants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose (first dose was administered at dose level 2 while second and third doses were administered at dose level 3) along with IV infusion of durvalumab 1500 mg Q4W starting from Day 8 (on the same day of second dose of MEDI9253) until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. Receives: Biological: MEDI9253; 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, persistent or significant disability/incapacity, important medical event, congenital anomaly/birth defect (in the offspring of the subject). 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: Day 1 through 76.14 weeks (maximum observed duration)
Number of Participants With Dose-limiting Toxicities (DLTs)
DLT: Any study drug-related Grade (G) 3 or higher toxicity; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) together with total bilirubin (TBL) ≥ 2 × ULN; Grade ≥ 2 myocarditis; Grade 2 non-infectious pneumonitis that does not resolve to ≤ G 1 within 7 days; any ≥ G 2 MEDI9253-related toxicity that prevents the administration of more than 1 dose of MEDI9253; in the sequential dosing cohorts, any ≥ Grade 2 MEDI9253-related toxicity that prevents administration of the first dose of durvalumab; any AE that after consultation with the sponsor and investigators, is deemed to be a DLT.
Measured: From the first dose of MEDI9253 through Day 14 (single dose cohorts) or Day 28 (multiple dose cohorts)
Number of Participants With TEAEs Leading to Discontinuation
Participants were permanently discontinued (PED) due to TEAE if: an AE that in the opinion of the investigator or the sponsor, warrants discontinuation of further dosing; an AE that met the criteria for a DLT during the DLT-evaluation period (from the first dose of MEDI9253 through Day 14 [single dose cohorts] or Day 28 [multiple dose cohorts]) unless criteria for initiation of durvalumab are met; an AE that required permanent discontinuation of study drug per toxicity management guidelines.
Measured: Day 1 through 76.14 weeks (maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, pulse oximetry [on MEDI9253 dosing days only], pulse rate, and respiratory rate).
Measured: Day 1 through 76.14 weeks (maximum observed duration)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, coagulation, and urinalysis.
Measured: Day 1 through 76.14 weeks (maximum observed duration)
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs
Number of participants with abnormal ECG reported as TEAEs are reported.
Measured: Day 1 through 76.14 weeks (maximum observed duration)
Number of Participants With Abnormal Physical Examination Reported as TEAEs
Number of participants with abnormal physical examination reported as TEAEs are reported.
Measured: Day 1 through 76.14 weeks (maximum observed duration)
Secondary outcomes (13)
Percentage of Participants With Objective Response (OR) According to 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 criteria that occurs prior to the initiation of subsequent anticancer treatment and prior to progression. The CR is defined as disappearance of all target lesions (TLs) and non-target lesions (NTLs) present at baseline, any pathological lymph nodes selected as TLs or non-pathological lymph nodes of NTLs must have a reduction in short axis to < 10mm. The PR is defined as at least a 30% decrease in the sum of diameters of TLs, taking as reference the baseline sum of diameters as long as criteria for progressive disease (PD) are not met. PD is defined as "≥ 20% increase in the sum of diameters of TLs and an absolute increase of ≥ 5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters and unequivocal progression of existing NTLs. Percentage of participants with OR is reported.
Measured: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Time to Response (TTR) According to RECIST V1.1
The TTR is defined as the time from first dose until the first documentation of a subsequently confirmed OR. The OR is defined as confirmed CR or PR based on RECIST v1.1 criteria that occurs prior to the initiation of subsequent anticancer treatment and prior to progression. Only participants who have achieved confirmed CR or PR were evaluated for TTR. TTR was assessed using Kaplan-Meier methods.
Measured: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Percentage of Participants With Disease Control Rate (DCR) at 16 Weeks According to RECIST v1.1
The DCR at 16 weeks is defined as a best overall response of confirmed CR or PR or having stable disease (SD) (without subsequent cancer therapy) maintained for ≥ 15 weeks from first dose. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as a ≥ 20% increase in the sum of diameters of TLs and an absolute increase of ≥ 5mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Percentage of participants who have disease control at 16 weeks is reported.
Measured: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Progression Free Survival (PFS) According to RECIST v1.1
The PFS is defined as the time from first dose until the date of first documented PD or death (by any cause in the absence of disease progression), regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy. Median number of months of PFS assessed via Kaplan-Meier method is reported. Here, number of participants analyzed denotes those participants who had PFS event.
Measured: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Overall Survival (OS)
The OS is defined as the time from the date of first dose until death due to any cause regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy. Median number of months of OS assessed using Kaplan-Meier method is reported. Here, number of participants analyzed denotes those participants who had an event.
Measured: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Whole Blood Viral Genome Concentrations of MEDI9253 for Single Dose Cohorts
The whole blood viral genome concentrations of MEDI9253 for single dose cohorts are reported.
Measured: Pre-dose, end of infusion (EOI); 1, 2, 4, 6, 9, 12, 24, 32, 40, 48, 72 hours and Days 7, 14, 21, 42 post EOI in Cycle 1 (each cycle is 28 days); and Durvalumab Cycle 3 pre-dose
Whole Blood Viral Genome Concentrations of MEDI9253 for Multiple Dose Cohorts
The whole blood viral genome concentrations of MEDI9253 for multiple dose cohorts are reported.
Measured: Pre-dose, end of infusion, 1 day post dose on Days 1, 8, and 15; and 7 days post Dose 3; Durvalumab Cycle 1 (each cycle is 28 days)-Days 29, 36; Cycle 2-Days 36, 57; Cycle 3 Pre-dose Days 64, 85
Plasma Interleukin (IL)-12 Concentrations for Single Dose Cohorts
The plasma IL-12 concentrations for single dose cohorts are reported.
Measured: Pre-dose, 1, 2, 4, 6, 9, 12, 24, 32, 40, 48, 72 hours and Days 7, 14, 21, 42 post end of infusion, and Durvalumab Cycle 3 (each cycle is 28 days) pre-dose
Plasma IL-12 Concentrations for Multiple Dose Cohorts
The plasma IL-12 concentrations for multiple dose cohorts are reported.
Measured: Pre-dose, end of infusion, 1 day post dose on Days 1, 8, and 15; and 7 days post Dose 3; Durvalumab Cycle 1 (each cycle is 28 days)-Days 29, 36; Cycle 2-Days 36, 57; Cycle 3 Pre-dose Days 64, 85
Cluster of differentiation (CD) 8 T cell Density as Assessed by Immunohistochemistry (IHC)
The mean CD8 T cell density by IHC is reported.
Measured: Baseline (Day -28 to -Day 1) and on Days 8, 15, 36, and 57
Percentage of Programmed Cell Death Ligand 1 (PD-L1) Positive Tumor Cells by IHC
The percentage of PD-L1 positive tumor cells by IHC is reported.
Measured: Baseline (Day -28 to -Day 1) and on Days 8, 15, 36, and 57
Percentage of Combined Tumor and Immune PD-L1 Positive Tumor Cells in Tumor Areas as Assessed by IHC
The percentage of combined tumor and immune PD-L1 positive tumor cells in tumor areas as assessed by IHC is reported.
Measured: Baseline (Day -28 to -Day 1) and on Days 8, 15, 36, and 57
Number of Participants with Positive Neutralizing Antibody (nAb) Response to MEDI9253
Number of participants with positive nAb response to MEDI9253 is reported. Persistent positive is defined as positive at ≥ 2 post-baseline assessments (with ≥ 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is complement of persistent positive. Treatment boosted nAb is defined as baseline nAb titer that was boosted to a 4-fold or higher-level following study drug administration. Treatment emergent nAb is defined as the sum of treatment-induced nAb (post-baseline positive only) and treatment-boosted nAb.
Measured: Baseline (pre-dose Day 1), Cycle 1 (each cycle is 28 days) Day 22, Cycle 2 Day 1, Cycle 3 Day 1, and 28 days after the last dose (7.47 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2020
- Study start2 Dec 2020
- Primary completion31 May 2024
- Study completion31 May 2024
Why it stopped: The study was terminated early due to lack of efficacy and absence of biomarker evidence of MEDI9253's impact on the tumors.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04613492
- Sponsor's protocol ID
- D7880C00001
- Other IDs
- 2020-002294-96
- Status last verified
- Jun 2025
- First submitted
- 28 Oct 2020
- Last updated
- 24 Jun 2025
- Results posted
- 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2025. 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 MEDI9253, a Recombinant Newcastle Disease Virus Encoding Interleukin-12, in Combination With Durvalumab in Participants With Select Advanced/Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT04613492
- Acronym / sponsor ID
- D7880C00001
- Conditions
- Solid Tumors
- Keywords
- Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to lack of efficacy and absence of biomarker evidence of MEDI9253's impact on the tumors.
- Enrolment
- 40 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 2 Dec 2020 (actual)
- Primary completion
- 31 May 2024 (actual)
- Study completion
- 31 May 2024 (actual)
- First posted
- 3 Nov 2020 (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.
Study D7880C00001 is a first-in-human (FIH), Phase 1, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of MEDI9253 in combination with durvalumab in adult participants with select advanced/metastatic solid tumors.
Detailed description
Up to approximately 192 participants may be assigned to study intervention in the study across approximately 30 sites globally.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| MEDI9253 Single Dose Level 1 + Durvalumab 1500 mg Q4W | Experimental | Biological: MEDI9253, Biological: DurvalumabParticipants will receive intravenous (IV) infusion of a single dose of MEDI9253 dose level 1 on Day 1. After 14 days (+7 days) of MEDI9253 dose, participants will receive IV durvalumab at 1500 mg once every 4 weeks (Q4W) until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. |
| MEDI9253 Single Dose Level 2 + Durvalumab 1500 mg Q4W | Experimental | Biological: MEDI9253, Biological: DurvalumabParticipants will receive IV infusion of a single dose of MEDI9253 dose level 2 on Day 1. After 14 days (+7 days) of MEDI9253 dose, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. |
| MEDI9253 Multiple Dose Level 2 + Durvalumab 1500 mg Q4W | Experimental | Biological: MEDI9253, Biological: DurvalumabParticipants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 2 over a maximum of 17 days, with a minimum of 5 days between each dose. After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. |
| MEDI9253 Multiple Dose Level 3 + Durvalumab 1500 mg Q4W | Experimental | Biological: MEDI9253, Biological: DurvalumabParticipants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose. After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. |
| MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Seq 3A-DESENS | Experimental | Biological: MEDI9253, Biological: DurvalumabParticipants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose (first dose was administered at dose level 2 while second and third doses were administered at dose level 3). After 14 days (+7 days) post the last dose of MEDI9253, participants will receive IV durvalumab at 1500 mg Q4W until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. |
| MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Conc3B-DESENS | Experimental | Biological: MEDI9253, Biological: DurvalumabParticipants will receive IV infusion of 3 weekly doses (±2 days) of MEDI9253 dose level 3 over a maximum of 17 days, with a minimum of 5 days between each dose (first dose was administered at dose level 2 while second and third doses were administered at dose level 3) along with IV infusion of durvalumab 1500 mg Q4W starting from Day 8 (on the same day of second dose of MEDI9253) until disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity, for up to 2 years. |
Who may qualify
- Ages
- 18 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Participant must be at least 18 years old at signing of informed consent.
- Body weight > 35 kg at screening.
Key exclusion criteria (2 listed)
- 1 Primary central nervous system (CNS) disease is excluded, as well as untreated or uncontrolled metastatic CNS involvement, leptomeningeal disease, or cord compression.
- NOTE: CNS disease that has been treated and stable/controlled for at least 3 months is permitted. Participants with CNS disease controlled via systemic steroids are not permitted.
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 |
|---|---|---|
| MEDI9253Participants will receive either single or multiple dose of MEDI9253; sequentially or concurrent with Durvalumab | Biological | MEDI9253 Multiple Dose Level 2 + Durvalumab 1500 mg Q4W, MEDI9253 Multiple Dose Level 3 + Durvalumab 1500 mg Q4W, MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Conc3B-DESENS, MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Seq 3A-DESENS, MEDI9253 Single Dose Level 1 + Durvalumab 1500 mg Q4W, MEDI9253 Single Dose Level 2 + Durvalumab 1500 mg Q4W |
| DurvalumabParticipants will receive durvalumab treatment sequentially or concurrently with MEDI9253 | Biological | MEDI9253 Multiple Dose Level 2 + Durvalumab 1500 mg Q4W, MEDI9253 Multiple Dose Level 3 + Durvalumab 1500 mg Q4W, MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Conc3B-DESENS, MEDI9253 Multiple Dose Level 3+Durva 1500 mg Q4W Seq 3A-DESENS, MEDI9253 Single Dose Level 1 + Durvalumab 1500 mg Q4W, MEDI9253 Single Dose Level 2 + Durvalumab 1500 mg Q4W |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: Day 1 through 76.14 weeks (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, persistent or significant disability/incapacity, important medical event, congenital anomaly/birth defect (in the offspring of the subject). 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 (DLTs)
Time frame: From the first dose of MEDI9253 through Day 14 (single dose cohorts) or Day 28 (multiple dose cohorts)
DLT: Any study drug-related Grade (G) 3 or higher toxicity; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) together with total bilirubin (TBL) ≥ 2 × ULN; Grade ≥ 2 myocarditis; Grade 2 non-infectious pneumonitis that does not resolve to ≤ G 1 within 7 days; any ≥ G 2 MEDI9253-related toxicity that prevents the administration of more than 1 dose of MEDI9253; in the sequential dosing cohorts, any ≥ Grade 2 MEDI9253-related toxicity that prevents administration of the first dose of durvalumab; any AE that after consultation with the sponsor and investigators, is deemed to be a DLT.
Number of Participants With TEAEs Leading to Discontinuation
Time frame: Day 1 through 76.14 weeks (maximum observed duration)
Participants were permanently discontinued (PED) due to TEAE if: an AE that in the opinion of the investigator or the sponsor, warrants discontinuation of further dosing; an AE that met the criteria for a DLT during the DLT-evaluation period (from the first dose of MEDI9253 through Day 14 [single dose cohorts] or Day 28 [multiple dose cohorts]) unless criteria for initiation of durvalumab are met; an AE that required permanent discontinuation of study drug per toxicity management guidelines.
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Time frame: Day 1 through 76.14 weeks (maximum observed duration)
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, pulse oximetry [on MEDI9253 dosing days only], pulse rate, and respiratory rate).
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Time frame: Day 1 through 76.14 weeks (maximum observed duration)
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, coagulation, and urinalysis.
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs
Time frame: Day 1 through 76.14 weeks (maximum observed duration)
Number of participants with abnormal ECG reported as TEAEs are reported.
Number of Participants With Abnormal Physical Examination Reported as TEAEs
Time frame: Day 1 through 76.14 weeks (maximum observed duration)
Number of participants with abnormal physical examination reported as TEAEs are reported.
13 secondary outcomes
Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Time frame: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Time to Response (TTR) According to RECIST V1.1
Time frame: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Percentage of Participants With Disease Control Rate (DCR) at 16 Weeks According to RECIST v1.1
Time frame: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Progression Free Survival (PFS) According to RECIST v1.1
Time frame: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Overall Survival (OS)
Time frame: Baseline (Days -28 to -1) through 90 days post last dose (76.14 weeks)
Whole Blood Viral Genome Concentrations of MEDI9253 for Single Dose Cohorts
Time frame: Pre-dose, end of infusion (EOI); 1, 2, 4, 6, 9, 12, 24, 32, 40, 48, 72 hours and Days 7, 14, 21, 42 post EOI in Cycle 1 (each cycle is 28 days); and Durvalumab Cycle 3 pre-dose
Whole Blood Viral Genome Concentrations of MEDI9253 for Multiple Dose Cohorts
Time frame: Pre-dose, end of infusion, 1 day post dose on Days 1, 8, and 15; and 7 days post Dose 3; Durvalumab Cycle 1 (each cycle is 28 days)-Days 29, 36; Cycle 2-Days 36, 57; Cycle 3 Pre-dose Days 64, 85
Plasma Interleukin (IL)-12 Concentrations for Single Dose Cohorts
Time frame: Pre-dose, 1, 2, 4, 6, 9, 12, 24, 32, 40, 48, 72 hours and Days 7, 14, 21, 42 post end of infusion, and Durvalumab Cycle 3 (each cycle is 28 days) pre-dose
Plasma IL-12 Concentrations for Multiple Dose Cohorts
Time frame: Pre-dose, end of infusion, 1 day post dose on Days 1, 8, and 15; and 7 days post Dose 3; Durvalumab Cycle 1 (each cycle is 28 days)-Days 29, 36; Cycle 2-Days 36, 57; Cycle 3 Pre-dose Days 64, 85
Cluster of differentiation (CD) 8 T cell Density as Assessed by Immunohistochemistry (IHC)
Time frame: Baseline (Day -28 to -Day 1) and on Days 8, 15, 36, and 57
Percentage of Programmed Cell Death Ligand 1 (PD-L1) Positive Tumor Cells by IHC
Time frame: Baseline (Day -28 to -Day 1) and on Days 8, 15, 36, and 57
Percentage of Combined Tumor and Immune PD-L1 Positive Tumor Cells in Tumor Areas as Assessed by IHC
Time frame: Baseline (Day -28 to -Day 1) and on Days 8, 15, 36, and 57
Number of Participants with Positive Neutralizing Antibody (nAb) Response to MEDI9253
Time frame: Baseline (pre-dose Day 1), Cycle 1 (each cycle is 28 days) Day 22, Cycle 2 Day 1, Cycle 3 Day 1, and 28 days after the last dose (7.47 weeks)
Results and safety
The study was stopped early (reason given: The study was terminated early due to lack of efficacy and absence of biomarker evidence of MEDI9253's impact on the tumors.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2025.
- Redacted CSR SynopsisLink 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Related trials for Solid Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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.
The record lists no contact. Use the official record to reach the sponsor.
8 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 MEDI9253 and Durvalumab in people with Solid Tumors, run by AstraZeneca at 8 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 2 inclusion and 2 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: stopped early, as of the sponsor's last update on 24 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, France. 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 was stopped early (reason given: The study was terminated early due to lack of efficacy and absence of biomarker evidence of MEDI9253's impact on the tumors.). Results are not available in the source record.
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: Day 1 through 76.14 weeks (maximum observed duration)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jun 2025.