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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

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ClinicalTrials.gov Identifier: NCT02556463
Recruitment Status : Recruiting
First Posted : September 22, 2015
Last Update Posted : February 2, 2018
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
To evaluate MEDI9197 when administered by intratumoral injection to subjects with solid tumors or CTCL, and in combination with durvalumab and/or palliative radiation in subjects with solid tumors.

Condition or disease Intervention/treatment Phase
Solid Tumors CTCL Cancer Drug: MEDI9197 Biological: durvalumab Radiation: radiation Phase 1

Detailed Description:
This is a multicenter, unblinded study to evaluate the TLR 7/8 agonist MEDI9197 delivered by IT injection to subjects with solid tumors or CTCL, and in combination with durvalumab and/or palliative radiation in subjects with solid tumors. The study uses a 3 + 3 dose escalation design to evaluate a range of doses.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 4, 2015
Estimated Primary Completion Date : August 19, 2020
Estimated Study Completion Date : August 19, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Escalation MEDI9197
MEDI9197
Drug: MEDI9197
Subjects will receive MEDI9197 every 4 weeks

Experimental: Escalation MEDI9197 with durvalumab
MEDI9197 in combination with durvalumab
Drug: MEDI9197
Subjects will receive MEDI9197 every 4 weeks

Biological: durvalumab
Subjects will receive durvalumab every 4 weeks
Other Name: MEDI4736

Experimental: Escalation MEDI9197 durvalumab radiation
MEDI9197 in combination with durvalumab and palliative radiation
Drug: MEDI9197
Subjects will receive MEDI9197 every 4 weeks

Biological: durvalumab
Subjects will receive durvalumab every 4 weeks
Other Name: MEDI4736

Radiation: radiation
palliative radiation every 4 weeks

Experimental: MEDI9197 with palliative radiation
MEDI9197 in combination with palliative radiation
Drug: MEDI9197
Subjects will receive MEDI9197 every 4 weeks

Radiation: radiation
palliative radiation every 4 weeks




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. The maximum concentration of MEDI9197 after the first injection [ Time Frame: Pre-dose to 24 hours post first dose ]
  2. The apparent terminal half-life of MEDI9197 [ Time Frame: Pre-dose to 24 hours post first dose ]
  3. Percent change from baseline in cluster of differentiation 8 tumor infiltrating lymphocytes in tumor tissue [ Time Frame: Baseline to Day 50 ]
  4. Percent change from baseline in serum inflammatory cytokine levels [ Time Frame: Pre-dose to end of study, up to 24 months ]
  5. Percent change from baseline in tumor measurements [ Time Frame: Pre-dose to disease progression, up to 12 months ]
  6. Objective response rate [ Time Frame: Pre-dose to end of study, up to 24 months ]
  7. Duration of response rate [ Time Frame: Pre-dose to end of study, up to 24 months ]
  8. Percent change from baseline in CAILDS for subjects with CTCL [ Time Frame: Pre-dose to disease progression, up to 12 months ]
  9. Percent change from baseline in SWAT scored for subjects with CTCL [ Time Frame: Pre-dose to disease progression, up to 12 months ]
  10. Percent change from baseline in Investigator Global Assessment (IGA) for subjects with CTCL [ Time Frame: Pre-dose to disease progression, up to 12 months ]
  11. Percent change from baseline in Subject Global Assessment (SGA) for subjects with CTCL [ Time Frame: Pre-dose to disease progression, up to 12 months ]


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects at least 18 years at the time of screening
  2. Adequate organ function within 14 days of enrollment confirmed by laboratory results
  3. Off immunosuppressive medications including, but not limited to, systemic corticosteroids at doses exceeding 10 mg/day prednisone or equivalent

Additional Inclusion Criteria for Part 1:

  1. Metastatic/locally advanced solid tumor malignancy that has progressed on, is refractory to, or for which there is no standard of care therapy
  2. At least one lesion that is easily accessible for injection (subjects enrolled prior to Amendment 3 only)
  3. At least one deep-seated lesion suitable for intervention (subjects enrolled in the deep-seated lesion expansion portion only)
  4. At least 2 lesions (for subjects enrolled to evaluate addition of concurrent palliative radiation to MEDI9197 therapy)

Additional Inclusion Criteria for Subjects in Part 2

  1. Clinical diagnosis of CTCL, including documentation of a skin biopsy with histological findings consistent with CTCL
  2. Stage IB, IIA or IIB disease: T1, T2 or T3 (patches, plaques or tumors) with measurable lesions
  3. Previous treatment with at least one standard therapy used to treat the stage of disease at study entry
  4. At least 2 lesions amenable to response assessment

Additional Inclusion Criteria for Subjects in Part 3A and 3B

1. Metastatic/locally advanced solid tumor malignancy that has progressed on, is refractory to, or for which there is no standard of care therapy

Exclusion Criteria:

Any of the following would exclude the subject from participation in the study:

  1. Subjects who have received prior immunotherapy are NOT permitted to enroll unless all of the following apply:

    1. Prior anti-CTLA 4 inhibitor last dose administered at least 100 days ago. Other prior immunotherapies, the last dose administered at least 28 days prior to planned first dose of MEDI9197
    2. Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
    3. All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or baseline prior to screening for this study. Must not have experienced a ≥ Grade 3 AE or neurologic, pneumonitis or ocular AE of any grade while receiving prior immunotherapy
    4. Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day
  2. Pregnant or lactating
  3. Active bacterial, fungal, or viral infections
  4. Active autoimmune disease, chronic inflammatory condition, conditions requiring concurrent use of any systemic immunosuppressants or steroids
  5. Immune-deficiency states - myelodysplastic disorders, marrow failures, human immunodeficiency virus (HIV) infection, history of solid organ transplant or bone marrow allograft, or recent pregnancy
  6. Requires continuous anticoagulation or antiplatelet therapy.
  7. History of coagulopathy resulting in uncontrolled bleeding.
  8. Rapidly progressing disease
  9. Untreated or uncontrolled central nervous system (CNS) involvement.
  10. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment
  11. 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 and laboratory values listed per inclusion criteria
  12. Chronic active hepatitis B or C
  13. Known allergy to sesame oil and/or nuts
  14. Cardiac exclusions: New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled hypertension, unstable angina pectoris, clinical important cardiac arrhythmia, mean QTC interval corrected for heart rate >500ms
  15. Major surgery within 4 weeks prior to study entry or still recovering from prior surgery
  16. Receipt of live, attenuated vaccine within 28 days prior to study entry.
  17. Receipt of any systemic anticancer therapy not mentioned above within the last 2 weeks or 5 half-lives
  18. Subjects with CTCL, must not have had prior therapy with Imiquimod, total body electron beam radiation, investigational drugs or treatments within 8 weeks. They must not have had prior therapy with local radiation, UBV therapy, PUVA, any topical chemotherapy, photopheresis, systemic retinoids, corticosteroids, immune response modifiers, IFN inducers, chemotherapeutic agents or biological agents or any topical treatment within 4 weeks. They must not have a known history or positive test for infection with HTLV-1.
  19. Cognitive disorder such that informed consent cannot be obtained directly from the subject
  20. Subjects who have previously participated in this study and received MEDI9197.
  21. Subjects who have received prior TLR agonists, both systemic and topical.
  22. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02556463


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
United States, California
Research Site Recruiting
San Francisco, California, United States, 94115
United States, Colorado
Research Site Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Research Site Withdrawn
Tampa, Florida, United States, 33612
United States, Minnesota
Research Site Recruiting
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Research Site Recruiting
New York, New York, United States, 10029
United States, North Carolina
Research Site Recruiting
Chapel Hill, North Carolina, United States, 27599-7305
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
Canada, Ontario
Research Site Recruiting
Toronto, Ontario, Canada, M5G 1Z6
France
Research Site Recruiting
Villejuif, France, 94805
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: MedImmune LLC MedImmune LLC

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02556463     History of Changes
Other Study ID Numbers: D6410C00001
First Posted: September 22, 2015    Key Record Dates
Last Update Posted: February 2, 2018
Last Verified: January 2018

Keywords provided by MedImmune LLC:
MEDI9197
TLR 7/8 Agonist
Durvalumab
MEDI4736
Imfinzi

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs