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Oleclumab (MEDI9447) EGFRm NSCLC Novel Combination Study

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: NCT03381274
Recruitment Status : Active, not recruiting
First Posted : December 21, 2017
Last Update Posted : May 6, 2020
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Study Description
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Brief Summary:
The objective of this study is to investigate the safety, tolerability and antitumor activity of novel combination therapies administered in subjects with advanced EGFRm NSCLC

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Biological: MEDI9447 Drug: Osimertinib Drug: AZD4635 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 98 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multiarm, Open-label, Multicenter, Phase 1b/2 Study to Evaluate Novel Combination Therapies in Subjects With Previously Treated Advanced EGFRm NSCLC
Actual Study Start Date : May 8, 2018
Estimated Primary Completion Date : December 12, 2022
Estimated Study Completion Date : December 12, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A
MEDI9447 and osimertinib
 Biological: MEDI9447
Subjects will receive MEDI9447 in combination with osimertinib or AZD4635 until disease progression

Drug: Osimertinib
Subjects will receive osimertinib in combination with MEDI9447 until disease progression
Experimental: Arm B
MEDI9447 and AZD4635
 Biological: MEDI9447
Subjects will receive MEDI9447 in combination with osimertinib or AZD4635 until disease progression

Drug: AZD4635
Subjects will receive AZD4635 in combination with MEDI9447 until disease progression


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Adverse Events as a measure of safety [ Time Frame: Screening through 90 days after last dose of investigational product ]
    The primary endpoint is safety as assessed by the presence of adverse events and serious adverse events

  2. Objective response rate as a measure of anti tumor activity in dose expansion phase [ Time Frame: During treatment through study completion, about 2 years after the last subject dosed ]
    The primary endpoint in dose expansion phase includes efficacy assessed by objective response


Secondary Outcome Measures :
  1. Duration of Response (DoR) [ Time Frame: During treatment through study completion, about 2 years after the last subject dosed ]
    The duration from the first documentation of objective response (OR) to the first documented disease progression or death due to any cause, whichever occurs first

  2. Disease Control (DC) [ Time Frame: During treatment through study completion, about 2 years after the last subject dosed ]
    Defined as complete response (CR), partial response (PR) or stable disease (SD)

  3. Progression Free Survival (PFS) [ Time Frame: During treatment through study completion, about 2 years after the last subject dosed ]
    From the start of treatment with investigational product until the first documentation of disease progression or death due to any cause, whichever occurs first.

  4. Overall Survival (OS) [ Time Frame: During treatment through study completion, about 2 years after the last subject dosed ]
    From the start of treatment with investigational product until death due to any cause

  5. Objective Response by T790M status [ Time Frame: During treatment through study completion, about 2 years after the last subject dosed ]
    Defined as best overall response of confirmed CR or confirmed PR according to RECIST version 1.1

  6. Disease Control by T790M status [ Time Frame: During treatment through study completion, about 2 years after the last subject dosed ]
    Defined as CR, PR or SD

  7. Serum MEDI9447 concentration levels [ Time Frame: During treatment through 90 days after last dose of investigational product ]
    Pharmacokinetic

  8. Serum Osimertinib concentration levels [ Time Frame: During treatment through 90 days after last dose of investigational product ]
    Pharmacokinetic

  9. Serum AZD4635 concentration levels [ Time Frame: During treatment through 90 days after last dose of investigational product ]
    Pharmacokinetic

  10. Development of detectable anti-drug antibody(ADA) to MEDI9447 [ Time Frame: During treatment through 90 days after last dose of investigational product ]
    Immunogenicity


Eligibility Criteria
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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.


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

Inclusion Criteria:

  1. Age ≥ 18
  2. ECOG Performance Status of 0 or 1
  3. Weight ≥ 35 kg

  4. Diagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFR mutation

    • For Arm A: must have received 1 prior line of therapy with an EGFR TKI and confirmed T790M negative
    • For Arm B: must have received at least 2 but not more than 4 prior lines of therapy.

Exclusion Criteria:

  1. Receipt of an EGFR TKI within 14 days of the first dose of study treatment.
  2. Receipt of any conventional or investigational anticancer therapy not otherwise specified within 21 days of the planned first dose.
  3. Prior receipt of any investigational immunotherapy. Subjects may have received agents that have local health authority approval for the disease indication
  4. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
  5. Subjects with a history of venous thrombosis within the past 3 months
  6. Subjects with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 6 months
  7. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
  8. Other invasive malignancy within 2 years.
  9. Untreated CNS metastatic disease, leptomeningeal disease, or cord compression
  10. Current or prior use of immunosuppressive medication within 14 days prior to the first dose

Additional Exclusion Criteria for Arm A

  1. Concurrent treatment (or inability to stop therapy) with medications or herbal supplements known to be potent inducers of CYP3A4
  2. Subject has a history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
  3. Subject requires continuous supplemental oxygen for any reason.

Additional Exclusion Criteria for Arm B

  1. Herbal preparations/medications are not allowed throughout the study
  2. History of seizures excluding those that occurred due to previously untreated CNS metastasis
Contacts and Locations
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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): NCT03381274


Locations
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United States, California
Research Site
La Jolla, California, United States, 92093
Research Site
San Francisco, California, United States, 94143
United States, Colorado
Research Site
Aurora, Colorado, United States, 80045
United States, Connecticut
Research Site
New Haven, Connecticut, United States, 06510
United States, Florida
Research Site
Gainesville, Florida, United States, 32608
United States, Georgia
Research Site
Atlanta, Georgia, United States, 30322
United States, Illinois
Research Site
Chicago, Illinois, United States, 60611
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21224
United States, New York
Research Site
New York, New York, United States, 10032
United States, Texas
Research Site
Houston, Texas, United States, 77030
Korea, Republic of
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 06351
Research Site
Seoul, Korea, Republic of, 138-736
Taiwan
Research Site
Taichung, Taiwan, 40705
Research Site
Taipei City, Taiwan, 10050
Sponsors and Collaborators
MedImmune LLC
Investigators
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Study Director: MedImmune LLC MedImmune LLC
More Information
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03381274    
Other Study ID Numbers: D6070C00004
First Posted: December 21, 2017    Key Record Dates
Last Update Posted: May 6, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
EGFR mutated, CD73, A2AR, oleclumab, MEDI9447, AZD4635, osimertinib, NSCLC, immunotherapy
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
 Lung Diseases
Respiratory Tract Diseases
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action