Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of MEDI1191 in Sequential and Concurrent Combination With Durvalumab in Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03946800
Recruitment Status : Active, not recruiting
First Posted : May 13, 2019
Last Update Posted : January 9, 2020
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
To evaluate MEDI1191 administered intratumorally in sequential and concurrent combination with intravenous durvalumab in patients with solid tumors.

Condition or disease Intervention/treatment Phase
Solid Tumors Cancer Biological: MEDI1191 Biological: Durvalumab Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 8, 2019
Estimated Primary Completion Date : March 1, 2027
Estimated Study Completion Date : March 1, 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: MEDI1191 escalation in combination with durvalumab
MEDI1191 escalation in sequential and concurrent combination with durvalumab
Biological: MEDI1191
Subjects will receive MEDI1191 (at least twice)

Biological: Durvalumab
Subject will receive durvalumab every 4 weeks

Experimental: MEDI1191 expansion in combination with durvalumab
MEDI1191 expansion in sequential and concurrent combination with durvalumab
Biological: MEDI1191
Subjects will receive MEDI1191 (at least twice)

Biological: Durvalumab
Subject will receive durvalumab every 4 weeks




Primary Outcome Measures :
  1. 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.

  2. 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).


Secondary Outcome Measures :
  1. 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). ]
    The occurrence of DLTs will be used to establish the maximum tolerated dose (MTD) of MEDI1191.

  2. Objective response rate (ORR) in advanced solid tumor subjects. [ 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).

  3. Disease Control Rate (DCR). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
    The DCR will be estimated by the proportion of disease control. Disease control is defined as CR, PR or stable disease.

  4. Duration of Response (DoR). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
    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.

  5. Time To Response (TTR). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years . ]
    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.

  6. Progression Free Survival (PFS). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
    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.

  7. Overall Survival (OS). [ Time Frame: Estimated to be from time of informed consent up to 3.5 years. ]
    OS will be measured from the start of treatment with investigational product until death due to any cause.

  8. 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. ]
    The endpoints for assessment of PK of MEDI1191 and durvalumab include individual MEDI1191 and durvalumab concentrations in serum at different timepoints after administration.

  9. 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. ]
    The endpoints for assessment of PK of MEDI1191 include MEDI1191 concentrations in serum at different timepoints after administration.

  10. Clearance of MEDI1191 [ Time Frame: From first dose of MEDI1191 through to 30 days after last dose of investigational product. ]
    The endpoints for assessment of PK of MEDI1191 include MEDI1191 concentrations in serum at different timepoints after administration.

  11. Immunogenicity of MEDI1191 [ Time Frame: From first dose of MEDI1191 through to 3.5 years after last dose of investigational product. ]
    The endpoints for assessment of immunogenicity of MEDI1191 include the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 101 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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 6 months after receipt of the final dose of investigational product.

Exclusion Criteria:

  • 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.
  • 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:

    1. Received only one dose of prior immunotherapy agent alone or as part of a combination regimen
    2. Experienced a toxicity that led to permanent discontinuation of prior immunotherapy
    3. All AEs while receiving prior immunotherapy did not resolve to ≤ Grade 1 or baseline prior to screening for this study.
    4. Experienced a ≥ Grade 3 AE (including pneumonitis) or neurologic, ocular, or cardiac AE of any grade while receiving prior immunotherapy.
    5. 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.

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): NCT03946800


Locations
Layout table for location information
United States, Arizona
Research Site
Tucson, Arizona, United States, 85724
United States, California
Research Site
La Jolla, California, United States, 92093
Research Site
Los Angeles, California, United States, 90025
Research Site
Los Angeles, California, United States, 90033
United States, Illinois
Research Site
Maywood, Illinois, United States, 60153
United States, New York
Research Site
Bronx, New York, United States, 10461
Research Site
Lake Success, New York, United States, 11042
Research Site
New York, New York, United States, 10017
Research Site
New York, New York, United States, 10029
United States, Rhode Island
Research Site
Providence, Rhode Island, United States, 02903
United States, Texas
Research Site
Houston, Texas, United States, 77030
United States, Washington
Research Site
Seattle, Washington, United States, 98109
Sponsors and Collaborators
MedImmune LLC
Investigators
Layout table for investigator information
Study Director: MedImmune LCC MedImmune LLC

Layout table for additonal information
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03946800    
Other Study ID Numbers: D8510C00001
First Posted: May 13, 2019    Key Record Dates
Last Update Posted: January 9, 2020
Last Verified: January 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
MEDI1191
Durvalumab
MEDI4736
Imfinzi
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Durvalumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs