Solid TumorsPhase 1NCT02556463
A Study of MEDI9197 in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors
A Phase 1 study testing MEDI9197 and durvalumab in people with Solid Tumors and CTCL, run by MedImmune LLC at 10 sites in 3 countries.
Trial summary
To evaluate MEDI9197 when administered by intratumoral injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Solid Tumors, CTCL, Cancer
- What is being tested?
- MEDI9197 and durvalumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 4 Nov 2015to 26 Oct 2018
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent and any locally required authorizations.
- Male and female subjects at least 18 years at the time of screening.
- Adequate organ function within 14 days of enrollment confirmed by laboratory results.
- Systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent.
- ECOG 0 or 1.
- Highly effective method of contraception from the date of the screening pregnancy test, and continued precautions for 6 months after the final dose of investigational product.
Show all 19Show fewer
- Baseline Child-Pugh Score of A1 to B7.
- Life expectancy ≥ 12 weeks, as estimated by Royal Marsden Hospital Score of 0 or 1 at baseline.
- Subjects with hepatocellular carcinoma (HCC) are eligible if the tumor is defined as nodular type 1 or 2 only.
- Additional Inclusion Criteria for Subjects in Parts 1 and 3
- Metastatic/locally advanced solid tumor malignancy that has progressed on, is refractory to, or for which there is no standard of care therapy.
- For subjects with cutaneous/subcutaneous lesions, subjects must have more than one measurable target lesion, at baseline, with a minimum of one lesion that meets protocol specified criteria.
- For subjects with deep-seated lesions, subjects must have more than one measurable target lesion at baseline (RECIST v1.1), with a minimum of one deep-seated lesion suitable for image-guided injection and that meets protocol specified criteria.
- Additional Inclusion Criteria for Subjects in Part 2 (Closed to Enrollment as of Protocol Amendment 6)
- Clinical diagnosis of CTCL, including documentation of a skin biopsy with histological findings consistent with CTCL or unconfirmed diagnosis of CTCL with confirmation biopsy at screening.
- Stage IB, IIA, or IIB disease: T1, T2 or T3 (patches, plaques or tumors) with measurable lesions.
- Previous treatment with at least one standard therapy used to treat the stage of disease at study entry; Stage IB, IIA or IIB CTCL.
- Measurable skin disease with at least 2 lesions amenable to response assessment.
- At least one lesion must be amenable to injection, ie, ≥ 1.5 cm in the longest diameter.
Who cannot join
- Any of the following would exclude the subject from participation in the study:
- Subjects who have received prior immunotherapy [(including but not limited to CTLA-4, oncolytic virus, oncolytic peptide-all require 100 day washout), programmed death ligand (PDL)-1, or programmed cell death 1 antagonists-both require 14 day washout)] are NOT permitted to enroll, with protocol exceptions.
- Pregnant or lactating.
- Active bacterial, fungal, or viral infections, including chronic or active hepatitis B, chronic or active hepatitis C, or active hepatitis A. Prior documented infections must have resolved.
- Active or prior documented autoimmune or inflammatory disorders, with exceptions per protocol. Includes known allergy to sesame oil and/or nuts.
- Immune-deficiency states - myelodysplastic disorders, marrow failures, human immunodeficiency virus (HIV) infection, history of solid organ transplant or bone marrow allograft, or recent pregnancy.
Show all 23Show fewer
- Requires continuous (daily) anticoagulation or antiplatelet therapy (including anti aggregants), acetylsalicylic acid (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs).
- History of coagulopathy resulting in uncontrolled bleeding or other bleeding disorders.
- Rapidly progressing disease per protocol.
- Untreated or uncontrolled central nervous system (CNS) involvement.
- Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment; with exceptions per protocol.
- Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1, with exception of alopecia, vitiligo.
- Uncontrolled concurrent illness.
- Cardiac exclusions: New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled hypertension, acute coronary syndrome within 6 months, clinical important cardiac arrhythmia, mean QTC interval corrected for heart rate >500ms.
- Major surgery within 4 weeks prior to study entry or still recovering from prior surgery.
- Receipt of live, attenuated vaccine within 28 days prior to study entry.
- Receipt of any systemic anticancer therapy not mentioned above within the last 2 weeks or 5 half-lives.
- Cognitive disorder such that informed consent cannot be obtained directly from the subject
- Subjects who have previously participated in this study and received MEDI9197, or concurrent enrollment in another clinical study involving an investigational treatment.
- Subjects who have received prior TLR agonists, both systemic and topical.
- Patients who have received prior therapeutic radiation within 28 days of dosing. All toxicities from prior radiotherapy must have resolved to ≤ Grade 1 or baseline prior to dosing.
- Body weight < 35 kg
- Subjects enrolling in Part 3 (ie, receiving durvalumab) must not have a history of interstitial lung disease or pneumonitis.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States8 sites
Research Site
Aurora, Colorado, 80045
Research Site
Chapel Hill, North Carolina, 27599-7305
Research Site
Houston, Texas, 77030
Research Site
Minneapolis, Minnesota, 55455
Research Site
New York, New York, 10029
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
San Francisco, California, 94115
Research Site
St Louis, Missouri, 63110
About this study
Official title: A Phase I, First-Time-in-Human Study of MEDI9197, a TLR 7/8 Agonist, Administered Intratumorally as a Single Agent in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors
To evaluate MEDI9197 when administered by intratumoral injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors.
Read the detailed description
This is a multicenter, open-label study to evaluate the TLR 7/8 agonist MEDI9197 delivered by IT injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors. The study has a dose escalation design using mTPI-2 to evaluate a range of doses.
- Conditions
- Solid Tumors, CTCL, Cancer
- Being tested
- MEDI9197, durvalumab
- Keywords
- MEDI9197, TLR 7/8 Agonist, 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.
MEDI9197Drug
Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)
durvalumabBiological
Also called MEDI4736
Subjects will receive durvalumab every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Escalation MEDI9197 | Experimental | MEDI9197 Receives: Drug: MEDI9197 |
| Escalation MEDI9197 with durvalumab | Experimental | MEDI9197 in combination with durvalumab Receives: Drug: MEDI9197; Biological: durvalumab |
| Escalation MEDI9197 durvalumab radiation | Experimental | MEDI9197 in combination with durvalumab and palliative radiation Receives: Drug: MEDI9197; Biological: durvalumab |
| MEDI9197 with palliative radiation | Experimental | MEDI9197 in combination with palliative radiation Receives: Drug: MEDI9197 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with solid tumor cancers
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
Measured: From time of informed consent through 4 weeks after last dose of investigational product
Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with CTCL
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
Measured: From time of informed consent through 6 months after last dose of investigational product
Safety & tolerability as determined by dose limiting toxicities and maximum tolerated or assessed dose of MEDI9197 administered by IT injection in combo with durvalumab and durvalumab plus palliative radiation to subjects with solid tumor cancers.
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
Measured: From time of informed consent through 90 days after last dose of investigational product
Secondary outcomes (11)
The maximum concentration of MEDI9197 after the first injection
Measured: Pre-dose to 24 hours post first dose
The apparent terminal half-life of MEDI9197
Measured: Pre-dose to 24 hours post first dose
Percent change from baseline in cluster of differentiation 8 tumor infiltrating lymphocytes in tumor tissue
Measured: Baseline to Day 50
Percent change from baseline in serum inflammatory cytokine levels
Measured: Pre-dose to end of study, up to 24 months
Percent change from baseline in tumor measurements
Measured: Pre-dose to disease progression, up to 12 months
Objective response rate
Measured: Pre-dose to end of study, up to 24 months
Duration of response
Measured: Pre-dose to end of study, up to 24 months
Percent change from baseline in CAILDS for subjects with CTCL
Measured: Pre-dose to disease progression, up to 12 months
Percent change from baseline in mSWAT scored for subjects with CTCL
Measured: Pre-dose to disease progression, up to 12 months
Percent change from baseline in Investigator Global Assessment (IGA) for subjects with CTCL
Measured: Pre-dose to disease progression, up to 12 months
Percent change from baseline in Subject Global Assessment (SGA) for subjects with CTCL
Measured: Pre-dose to disease progression, up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2015 (estimated)
- Study start4 Nov 2015
- Primary completion26 Oct 2018
- Study completion26 Oct 2018
Why it stopped: Company strategy
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
- 53 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
- NCT02556463
- Sponsor's protocol ID
- D6410C00001
- Status last verified
- Dec 2018
- First submitted
- 1 Sep 2015
- Last updated
- 19 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Siu L, Brody J, Gupta S, Marabelle A, Jimeno A, Munster P, Grilley-Olson J, Rook AH, Hollebecque A, Wong RKS, Welsh JW, Wu Y, Morehouse C, Hamid O, Walcott F, Cooper ZA, Kumar R, Ferte C, Hong DS. Safety and clinical activity of intratumoral MEDI9197 alone and in combination with durvalumab and/or palliative radiation therapy in patients with advanced solid tumors. J Immunother Cancer. 2020 Oct;8(2):e001095. doi: 10.1136/jitc-2020-001095.
PubMed 33037117
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, First-Time-in-Human Study of MEDI9197, a TLR 7/8 Agonist, Administered Intratumorally as a Single Agent in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors
- ClinicalTrials.gov ID
- NCT02556463
- Acronym / sponsor ID
- D6410C00001
- Conditions
- Solid Tumors, CTCL, Cancer
- Keywords
- MEDI9197, TLR 7/8 Agonist, Durvalumab, MEDI4736, Imfinzi
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company strategy
- Enrolment
- 53 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2015 (actual)
- Primary completion
- 26 Oct 2018 (actual)
- Study completion
- 26 Oct 2018 (actual)
- First posted
- 22 Sep 2015 (estimated)
- 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 MEDI9197 when administered by intratumoral injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors.
Detailed description
This is a multicenter, open-label study to evaluate the TLR 7/8 agonist MEDI9197 delivered by IT injection to subjects with solid tumors and in combination with durvalumab in 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
- 4
| Arm | Type | Receives |
|---|---|---|
| Escalation MEDI9197 | Experimental | Drug: MEDI9197MEDI9197 |
| Escalation MEDI9197 with durvalumab | Experimental | Drug: MEDI9197, Biological: durvalumabMEDI9197 in combination with durvalumab |
| Escalation MEDI9197 durvalumab radiation | Experimental | Drug: MEDI9197, Biological: durvalumabMEDI9197 in combination with durvalumab and palliative radiation |
| MEDI9197 with palliative radiation | Experimental | Drug: MEDI9197MEDI9197 in combination with palliative radiation |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Written informed consent and any locally required authorizations.
- Male and female subjects at least 18 years at the time of screening.
- Adequate organ function within 14 days of enrollment confirmed by laboratory results.
- Systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent.
- ECOG 0 or 1.
Key exclusion criteria (23 listed)
- Subjects who have received prior immunotherapy [(including but not limited to CTLA-4, oncolytic virus, oncolytic peptide-all require 100 day washout), programmed death ligand (PDL)-1, or programmed cell death 1 antagonists-both require 14 day washout)] are NOT permitted to enroll, with protocol exceptions.
- Pregnant or lactating.
- Active bacterial, fungal, or viral infections, including chronic or active hepatitis B, chronic or active hepatitis C, or active hepatitis A. Prior documented infections must have resolved.
- Active or prior documented autoimmune or inflammatory disorders, with exceptions per protocol. Includes known allergy to sesame oil and/or nuts.
- Immune-deficiency states - myelodysplastic disorders, marrow failures, human immunodeficiency virus (HIV) infection, history of solid organ transplant or bone marrow allograft, or recent pregnancy.
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 |
|---|---|---|
| MEDI9197Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6) | Drug | Escalation MEDI9197, Escalation MEDI9197 durvalumab radiation, Escalation MEDI9197 with durvalumab, MEDI9197 with palliative radiation |
| durvalumabAlso: MEDI4736Subjects will receive durvalumab every 4 weeks | Biological | Escalation MEDI9197 durvalumab radiation, Escalation MEDI9197 with durvalumab |
Primary outcome
Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with solid tumor cancers
Time frame: From time of informed consent through 4 weeks after last dose of investigational product
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with CTCL
Time frame: From time of informed consent through 6 months after last dose of investigational product
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
Safety & tolerability as determined by dose limiting toxicities and maximum tolerated or assessed dose of MEDI9197 administered by IT injection in combo with durvalumab and durvalumab plus palliative radiation to subjects with solid tumor cancers.
Time frame: From time of informed consent through 90 days after last dose of investigational product
The primary endpoint will be the number (%) of subjects with dose-limiting toxicities, adverse and serious adverse events and other safety parameters.
11 secondary outcomes
The maximum concentration of MEDI9197 after the first injection
Time frame: Pre-dose to 24 hours post first dose
The apparent terminal half-life of MEDI9197
Time frame: Pre-dose to 24 hours post first dose
Percent change from baseline in cluster of differentiation 8 tumor infiltrating lymphocytes in tumor tissue
Time frame: Baseline to Day 50
Percent change from baseline in serum inflammatory cytokine levels
Time frame: Pre-dose to end of study, up to 24 months
Percent change from baseline in tumor measurements
Time frame: Pre-dose to disease progression, up to 12 months
Objective response rate
Time frame: Pre-dose to end of study, up to 24 months
Duration of response
Time frame: Pre-dose to end of study, up to 24 months
Percent change from baseline in CAILDS for subjects with CTCL
Time frame: Pre-dose to disease progression, up to 12 months
Percent change from baseline in mSWAT scored for subjects with CTCL
Time frame: Pre-dose to disease progression, up to 12 months
Percent change from baseline in Investigator Global Assessment (IGA) for subjects with CTCL
Time frame: Pre-dose to disease progression, up to 12 months
Percent change from baseline in Subject Global Assessment (SGA) for subjects with CTCL
Time frame: Pre-dose to disease progression, up to 12 months
Results and safety
The study was stopped early (reason given: Company strategy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2018.
- Derived from this study: PubMed 33037117Siu L, Brody J, Gupta S, Marabelle A, Jimeno A, Munster P, Grilley-Olson J, Rook AH, Hollebecque A, Wong RKS, Welsh JW, Wu Y, Morehouse C, Hamid O, Walcott F, Cooper ZA, Kumar R, Ferte C, Hong DS. Safety and clinical activity of intratumoral MEDI9197 alone and in combination with durvalumab and/or palliative radiation therapy in patients with advanced solid tumors. J Immunother Cancer. 2020 Oct;8(2):e001095. doi: 10.1136/jitc-2020-001095.
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.
MedImmune LLC study director
MedImmune LLC
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MEDI9197 and durvalumab in people with Solid Tumors and CTCL, run by MedImmune LLC at 10 sites in 3 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 19 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: stopped early, as of the sponsor's last update on 19 Dec 2018. 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, Canada, 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: Company strategy). 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?
Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of MEDI9197 when administered by intratumoral injection to subjects with solid tumor cancers (time frame: From time of informed consent through 4 weeks after last dose of investigational product). The study lists 3 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 NCT02556463, 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 19 Dec 2018.