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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 : Terminated (Company strategy)
First Posted : September 22, 2015
Last Update Posted : December 18, 2018
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
To evaluate MEDI9197 when administered by intratumoral injection to subjects with solid tumors and in combination with durvalumab in subjects with solid tumors.

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

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 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
Actual Primary Completion Date : October 26, 2018
Actual Study Completion Date : October 26, 2018

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) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)

Experimental: Escalation MEDI9197 with durvalumab
MEDI9197 in combination with durvalumab
Drug: MEDI9197
Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)

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) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)

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

Experimental: MEDI9197 with palliative radiation
MEDI9197 in combination with palliative radiation
Drug: MEDI9197
Subjects will receive MEDI9197 (every 4 weeks) as monotherapy (or MEDI9197 every 8 weeks + durvalumab every 4 weeks)(PA6)




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 [ 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 mSWAT 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 ]


Information from the National Library of Medicine

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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 for All Subjects (Parts 1, 2 and 3)

  1. Written informed consent and any locally required authorizations.
  2. Male and female subjects at least 18 years at the time of screening.
  3. Adequate organ function within 14 days of enrollment confirmed by laboratory results.
  4. Systemic corticosteroids at doses exceeding 12 mg/day prednisone or equivalent.
  5. ECOG 0 or 1.
  6. 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.
  7. Baseline Child-Pugh Score of A1 to B7.
  8. Life expectancy ≥ 12 weeks, as estimated by Royal Marsden Hospital Score of 0 or 1 at baseline.
  9. 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

  10. Metastatic/locally advanced solid tumor malignancy that has progressed on, is refractory to, or for which there is no standard of care therapy.
  11. 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.
  12. 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)

  13. 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.
  14. Stage IB, IIA, or IIB disease: T1, T2 or T3 (patches, plaques or tumors) with measurable lesions.
  15. Previous treatment with at least one standard therapy used to treat the stage of disease at study entry; Stage IB, IIA or IIB CTCL.
  16. Measurable skin disease with at least 2 lesions amenable to response assessment.
  17. At least one lesion must be amenable to injection, ie, ≥ 1.5 cm in the longest diameter.

Exclusion Criteria:

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

  1. 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.
  2. Pregnant or lactating.
  3. 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.
  4. Active or prior documented autoimmune or inflammatory disorders, with exceptions per protocol. Includes known allergy to sesame oil and/or nuts.
  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 (daily) anticoagulation or antiplatelet therapy (including anti aggregants), acetylsalicylic acid (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs).
  7. History of coagulopathy resulting in uncontrolled bleeding or other bleeding disorders.
  8. Rapidly progressing disease per protocol.
  9. Untreated or uncontrolled central nervous system (CNS) involvement.
  10. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment; with exceptions per protocol.
  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.
  12. Uncontrolled concurrent illness.
  13. 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.
  14. Major surgery within 4 weeks prior to study entry or still recovering from prior surgery.
  15. Receipt of live, attenuated vaccine within 28 days prior to study entry.
  16. Receipt of any systemic anticancer therapy not mentioned above within the last 2 weeks or 5 half-lives.
  17. Cognitive disorder such that informed consent cannot be obtained directly from the subject
  18. Subjects who have previously participated in this study and received MEDI9197, or concurrent enrollment in another clinical study involving an investigational treatment.
  19. Subjects who have received prior TLR agonists, both systemic and topical.
  20. 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.
  21. Body weight < 35 kg
  22. Subjects enrolling in Part 3 (ie, receiving durvalumab) must not have a history of interstitial lung disease or pneumonitis.

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


Locations
United States, California
Research Site
San Francisco, California, United States, 94115
United States, Colorado
Research Site
Aurora, Colorado, United States, 80045
United States, Minnesota
Research Site
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63110
United States, New York
Research Site
New York, New York, United States, 10029
United States, North Carolina
Research Site
Chapel Hill, North Carolina, United States, 27599-7305
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Research Site
Houston, Texas, United States, 77030
Canada, Ontario
Research Site
Toronto, Ontario, Canada, M5G 1Z6
France
Research Site
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: December 18, 2018
Last Verified: December 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