Solid TumorsPhase 1NCT03946800
A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors
A Phase 1 study testing MEDI1191 and Durvalumab in people with Solid Tumors and Cancer, run by MedImmune LLC at 11 sites in 2 countries.
Trial summary
To evaluate MEDI1191 administered intratumorally in sequential and concurrent combination with intravenous durvalumab in patients with solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 101 years
- Conditions the study is for
- Solid Tumors, Cancer
- What is being tested?
- MEDI1191 and Durvalumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 8 May 2019to 24 Aug 2023
- 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
- ECOG 0 to 1.
- Adequate organ function within 2 weeks of starting study treatment.
- Prior to the first dose of MEDI1191, subjects with central nervous system (CNS) metastases must have been treated and must be asymptomatic.
- Cessation of systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent, methotrexate, azathioprine, ustekinumab (Stelara®), and tumor necrosis factor (TNF)-α/IL-6 blockers for at least 7 days prior to the first dose of MEDI1191.
- Subjects must have at least one lesion suitable for intratumoral dosing for superficial lesions but at least two lesion suitable for intratumoral dosing for deep-seated lesions.
- Subjects must have at least one non-injected lesion that can be measured by RECIST v1.1.
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- Histologic or cytologic confirmation of advanced solid tumor.
- Received and have progressed on or refractory to at least 1 line of standard systemic therapy in the recurrent/metastatic setting.
- Highly effective method of contraception from screening, and must agree to continue using such precautions for 3 months after the final dose of investigational product.
- Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from Day 1 through 3 months after receipt of the final dose of investigational product.
Who cannot join
- Subjects who have received prior IL-12 either alone or as part of a treatment regimen.
- Subjects who were administered any live attenuated vaccines within 30 days prior to first MEDI1191 injection.
- Known allergy or hypersensitivity to any component of MEDI1191 or durvalumab formulations.
- Active or prior documented autoimmune disorders within the past 5 years prior to the first scheduled dose of study treatment except alopecia, hypothyroidism (stable of hormone replacement), chronic skin condition (does not require systemic therapy), and celiac disease (controlled by diet alone).
- Immune-deficiency states - myelodysplastic disorders, marrow failure states, human immunodeficiency virus infection, history of solid organ transplant, bone marrow allograft, or active tuberculosis.
- History of coagulopathy resulting in uncontrolled bleeding or other bleeding disorders.
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- Require continuous anticoagulation or antiplatelet therapy (except for ≤ 100 mg acetylsalicylic acid [ASA]) which cannot be interrupted for more than 7 days for IT delivery of MEDI1191.
- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for cancer.
- Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 7 days prior to the first dose of study treatment. For subjects who have received prior immunotherapy, the following additional exclusion criteria apply:
- Received only one dose of prior immunotherapy agent alone or as part of a combination regimen
- Experienced a toxicity that led to permanent discontinuation of prior immunotherapy
- All AEs while receiving prior immunotherapy did not resolve to ≤ Grade 1 or baseline prior to screening for this study.
- Experienced a ≥ Grade 3 AE (including pneumonitis) or neurologic, ocular, or cardiac AE of any grade while receiving prior immunotherapy.
- Required the use of additional immunosuppression other than corticosteroids for the management of an AE, or experienced recurrence of an AE if re-challenged, or is currently requiring a maintenance dose of > 12 mg prednisone or equivalent per day.
- Any toxicity from prior therapy that has not completely resolved to ≤ Grade 1 or baseline at the time of consent.
- Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI1191, except intranasal, topical, inhaled corticosteroids, local steroid injections, systemic corticosteroids at physiologic doses not to exceed 12 mg/day of prednisone or equivalent, or steroids as premedication for hypersensitivity reactions.
- Cardiac exclusions: New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled hypertension, acute coronary syndrome within 6 months.
- Any condition that would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
- Uncontrolled intercurrent illness.
- Untreated, active hepatitis B or C.
- Major surgery within 4 weeks prior to first dose of MEDI1191 or still recovering from prior surgery.
- Subjects with untreated active major depression with suicidal ideation and/or plan.
- Female subjects who are pregnant, lactating, or intend to become pregnant during their participation in this study.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States8 sites
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093
Research Site
Los Angeles, California, 90025
Research Site
Los Angeles, California, 90089
Research Site
New York, New York, 10029
Research Site
New York, New York, 10065
Research Site
Providence, Rhode Island, 02903
Research Site
The Bronx, New York, 10461
Spain3 sites
Research Site
Barcelona, 08035
Research Site
Madrid, 28027
Research Site
Pamplona, 31008
About this study
Official title: A Phase 1, Open-label, Dose-escalation and Expansion Study of MEDI1191 Administered Intratumorally as Monotherapy and in Combination With Durvalumab in Subjects With Advanced Solid Tumors
To evaluate MEDI1191 administered intratumorally in sequential and concurrent combination with intravenous durvalumab in patients with solid tumors.
Read the detailed description
This is a multicenter, open-label study to evaluate MEDI1191 delivered by intratumoral injection in sequential and concurrent combination with intravenous durvalumab to subjects with solid tumors. The study has a dose escalation design using mTPI-2 to evaluate a range of doses.
- Conditions
- Solid Tumors, Cancer
- Being tested
- MEDI1191, Durvalumab
- Keywords
- MEDI1191, Durvalumab, MEDI4736, Imfinzi
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI1191Biological
Subjects will receive MEDI1191 (at least twice)
DurvalumabBiological
Subject will receive durvalumab every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| MEDI1191 escalation in combination with durvalumab | Experimental | MEDI1191 escalation in sequential and concurrent combination with durvalumab Receives: Biological: MEDI1191; Biological: Durvalumab |
| MEDI1191 expansion in combination with durvalumab | Experimental | MEDI1191 expansion in concurrent combination with durvalumab Receives: Biological: MEDI1191; Biological: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs).
The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI1191.
Measured: From time of informed consent until 90 days after the last dose of investigational product (MEDI1191 or durvalumab).
Objective response rate (ORR) in patients within expansion arms.
The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).
Measured: Estimated to be from time of informed consent up to 3.5 years.
Secondary outcomes (11)
Number of advanced solid tumor subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs).
The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI1191.
Measured: From time of informed consent until 90 days after the last dose of investigational product (MEDI1191 or durvalumab).
Objective response rate (ORR) in advanced solid tumor subjects.
The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).
Measured: Estimated to be from time of informed consent up to 3.5 years.
Disease Control Rate (DCR).
The DCR will be estimated by the proportion of disease control. Disease control is defined as CR, PR or stable disease.
Measured: Estimated to be from time of informed consent up to 3.5 years.
Duration of Response (DoR).
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.
Measured: Estimated to be from time of informed consent up to 3.5 years.
Time To Response (TTR).
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.
Measured: Estimated to be from time of informed consent up to 3.5 years .
Progression Free Survival (PFS).
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.
Measured: Estimated to be from time of informed consent up to 3.5 years.
Overall Survival (OS).
OS will be measured from the start of treatment with investigational product until death due to any cause.
Measured: Estimated to be from time of informed consent up to 3.5 years.
Maximum observed concentration (Cmax) of MEDI1191 and durvalumab
The endpoints for assessment of PK of MEDI1191 and durvalumab include individual MEDI1191 and durvalumab concentrations in serum at different timepoints after administration.
Measured: From first dose of MEDI1191 through to 30 days after last dose of investigational product.
Area under the concentration-time curve (AUC) of MEDI1191
The endpoints for assessment of PK of MEDI1191 include MEDI1191 concentrations in serum at different timepoints after administration.
Measured: From first dose of MEDI1191 through to 30 days after last dose of investigational product.
Clearance of MEDI1191
The endpoints for assessment of PK of MEDI1191 include MEDI1191 concentrations in serum at different timepoints after administration.
Measured: From first dose of MEDI1191 through to 30 days after last dose of investigational product.
Immunogenicity of MEDI1191
The endpoints for assessment of immunogenicity of MEDI1191 include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Measured: From first dose of MEDI1191 through to 3.5 years after last dose of investigational product.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start8 May 2019
- Primary completion24 Aug 2023
- Study completion24 Aug 2023
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 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
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MedImmune LCC, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03946800
- Sponsor's protocol ID
- D8510C00001
- Other IDs
- 2020-005784-31
- Status last verified
- Sep 2024
- First submitted
- 6 May 2019
- Last updated
- 2 Oct 2024
- 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Carneiro BA, Marron T, Zamarin D, Castanon E, Patel SP, Subbiah V, Mehmi I, El-Khoueiry A, Oberoi A, Abadier M, Jennings EC, Dubois V, Chen Z, Chen X, Elgeioushi N, Durham NM, Ridgway B, Fraenkel PG, Azaro A, Hamid O. Safety and efficacy of intratumoral MEDI1191, an IL-12 mRNA lipid nanoparticle, plus intravenous durvalumab in patients with advanced solid tumors: a first-in-human study. Clin Cancer Res. 2026 Aug 18. doi: 10.1158/1078-0432.CCR-25-4865. Online ahead of print.
PubMed 42611979
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Dose-escalation and Expansion Study of MEDI1191 Administered Intratumorally as Monotherapy and in Combination With Durvalumab in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03946800
- Acronym / sponsor ID
- D8510C00001
- Conditions
- Solid Tumors, Cancer
- Keywords
- MEDI1191, Durvalumab, MEDI4736, Imfinzi
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 8 May 2019 (actual)
- Primary completion
- 24 Aug 2023 (actual)
- Study completion
- 24 Aug 2023 (actual)
- First posted
- 13 May 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.
To evaluate MEDI1191 administered intratumorally in sequential and concurrent combination with intravenous durvalumab in patients with solid tumors.
Detailed description
This is a multicenter, open-label study to evaluate MEDI1191 delivered by intratumoral injection in sequential and concurrent combination with intravenous durvalumab to subjects with solid tumors. The study has a dose escalation design using mTPI-2 to evaluate a range of doses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MEDI1191 escalation in combination with durvalumab | Experimental | Biological: MEDI1191, Biological: DurvalumabMEDI1191 escalation in sequential and concurrent combination with durvalumab |
| MEDI1191 expansion in combination with durvalumab | Experimental | Biological: MEDI1191, Biological: DurvalumabMEDI1191 expansion in concurrent combination with durvalumab |
Who may qualify
- Ages
- 18 to 101 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ECOG 0 to 1.
- Adequate organ function within 2 weeks of starting study treatment.
- Prior to the first dose of MEDI1191, subjects with central nervous system (CNS) metastases must have been treated and must be asymptomatic.
- Cessation of systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent, methotrexate, azathioprine, ustekinumab (Stelara®), and tumor necrosis factor (TNF)-α/IL-6 blockers for at least 7 days prior to the first dose of MEDI1191.
- Subjects must have at least one lesion suitable for intratumoral dosing for superficial lesions but at least two lesion suitable for intratumoral dosing for deep-seated lesions.
Key exclusion criteria (23 listed)
- Subjects who have received prior IL-12 either alone or as part of a treatment regimen.
- Subjects who were administered any live attenuated vaccines within 30 days prior to first MEDI1191 injection.
- Known allergy or hypersensitivity to any component of MEDI1191 or durvalumab formulations.
- Active or prior documented autoimmune disorders within the past 5 years prior to the first scheduled dose of study treatment except alopecia, hypothyroidism (stable of hormone replacement), chronic skin condition (does not require systemic therapy), and celiac disease (controlled by diet alone).
- Immune-deficiency states - myelodysplastic disorders, marrow failure states, human immunodeficiency virus infection, history of solid organ transplant, bone marrow allograft, or active tuberculosis.
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 |
|---|---|---|
| MEDI1191Subjects will receive MEDI1191 (at least twice) | Biological | MEDI1191 escalation in combination with durvalumab, MEDI1191 expansion in combination with durvalumab |
| DurvalumabSubject will receive durvalumab every 4 weeks | Biological | MEDI1191 escalation in combination with durvalumab, MEDI1191 expansion in combination with durvalumab |
Primary outcome
Number of subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs).
Time frame: From time of informed consent until 90 days after the last dose of investigational product (MEDI1191 or durvalumab).
The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI1191.
Objective response rate (ORR) in patients within expansion arms.
Time frame: Estimated to be from time of informed consent up to 3.5 years.
The ORR is defined as the proportion of subjects with confirmed response (CR) or confirmed partial response (PR).
11 secondary outcomes
Number of advanced solid tumor subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs).
Time frame: From time of informed consent until 90 days after the last dose of investigational product (MEDI1191 or durvalumab).
Objective response rate (ORR) in advanced solid tumor subjects.
Time frame: Estimated to be from time of informed consent up to 3.5 years.
Disease Control Rate (DCR).
Time frame: Estimated to be from time of informed consent up to 3.5 years.
Duration of Response (DoR).
Time frame: Estimated to be from time of informed consent up to 3.5 years.
Time To Response (TTR).
Time frame: Estimated to be from time of informed consent up to 3.5 years .
Progression Free Survival (PFS).
Time frame: Estimated to be from time of informed consent up to 3.5 years.
Overall Survival (OS).
Time frame: Estimated to be from time of informed consent up to 3.5 years.
Maximum observed concentration (Cmax) of MEDI1191 and durvalumab
Time frame: From first dose of MEDI1191 through to 30 days after last dose of investigational product.
Area under the concentration-time curve (AUC) of MEDI1191
Time frame: From first dose of MEDI1191 through to 30 days after last dose of investigational product.
Clearance of MEDI1191
Time frame: From first dose of MEDI1191 through to 30 days after last dose of investigational product.
Immunogenicity of MEDI1191
Time frame: From first dose of MEDI1191 through to 3.5 years after last dose of investigational product.
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 2 Oct 2024.
- Derived from this study: PubMed 42611979Carneiro BA, Marron T, Zamarin D, Castanon E, Patel SP, Subbiah V, Mehmi I, El-Khoueiry A, Oberoi A, Abadier M, Jennings EC, Dubois V, Chen Z, Chen X, Elgeioushi N, Durham NM, Ridgway B, Fraenkel PG, Azaro A, Hamid O. Safety and efficacy of intratumoral MEDI1191, an IL-12 mRNA lipid nanoparticle, plus intravenous durvalumab in patients with advanced solid tumors: a first-in-human study. Clin Cancer Res. 2026 Aug 18. doi: 10.1158/1078-0432.CCR-25-4865. Online ahead of print.
- CRS Synopsis RedactedLink provided by the sponsor.
- Study ResultsLink 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.
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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 LCC study director
MedImmune LLC
11 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 MEDI1191 and Durvalumab in people with Solid Tumors and Cancer, run by MedImmune LLC at 11 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 10 inclusion and 23 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 2 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Spain. 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 subjects with adverse events (AEs) serious adverse events (SAEs) and dose limiting toxicities (DLTs). (time frame: From time of informed consent until 90 days after the last dose of investigational product (MEDI1191 or durvalumab).). The study lists 2 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 NCT03946800, 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 2 Oct 2024.