NCT03946800

Brief Summary

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
61

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started May 2019

Longer than P75 for phase_1

Geographic Reach
2 countries

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 6, 2019

Completed
2 days until next milestone

Study Start

First participant enrolled

May 8, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 13, 2019

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 24, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 24, 2023

Completed
Last Updated

October 2, 2024

Status Verified

September 1, 2024

Enrollment Period

4.3 years

First QC Date

May 6, 2019

Last Update Submit

September 30, 2024

Conditions

Keywords

MEDI1191DurvalumabMEDI4736Imfinzi

Outcome Measures

Primary Outcomes (2)

  • 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.

    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).

    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).

    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.

    Estimated to be from time of informed consent up to 3.5 years.

  • Disease Control Rate (DCR).

    Estimated to be from time of informed consent up to 3.5 years.

  • Duration of Response (DoR).

    Estimated to be from time of informed consent up to 3.5 years.

  • Time To Response (TTR).

    Estimated to be from time of informed consent up to 3.5 years .

  • +6 more secondary outcomes

Study Arms (2)

MEDI1191 escalation in combination with durvalumab

EXPERIMENTAL

MEDI1191 escalation in sequential and concurrent combination with durvalumab

Biological: MEDI1191Biological: Durvalumab

MEDI1191 expansion in combination with durvalumab

EXPERIMENTAL

MEDI1191 expansion in concurrent combination with durvalumab

Biological: MEDI1191Biological: Durvalumab

Interventions

MEDI1191BIOLOGICAL

Subjects will receive MEDI1191 (at least twice)

MEDI1191 escalation in combination with durvalumabMEDI1191 expansion in combination with durvalumab
DurvalumabBIOLOGICAL

Subject will receive durvalumab every 4 weeks

MEDI1191 escalation in combination with durvalumabMEDI1191 expansion in combination with durvalumab

Eligibility Criteria

Age18 Years - 101 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.
  • 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.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Research Site

La Jolla, California, 92093, United States

Location

Research Site

Los Angeles, California, 90025, United States

Location

Research Site

Los Angeles, California, 90089, United States

Location

Research Site

New York, New York, 10029, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

The Bronx, New York, 10461, United States

Location

Research Site

Providence, Rhode Island, 02903, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Madrid, 28027, Spain

Location

Research Site

Pamplona, 31008, Spain

Location

Related Links

MeSH Terms

Conditions

Neoplasms

Interventions

durvalumab

Study Officials

  • MedImmune LCC

    MedImmune LLC

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 6, 2019

First Posted

May 13, 2019

Study Start

May 8, 2019

Primary Completion

August 24, 2023

Study Completion

August 24, 2023

Last Updated

October 2, 2024

Record last verified: 2024-09

Data Sharing

IPD Sharing
Will share

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.

Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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