Clinical Trials /

Oleclumab (MEDI9447) EGFRm NSCLC Novel Combination Study

NCT03381274

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Oleclumab (MEDI9447) EGFRm NSCLC Novel Combination Study
  • Official Title: A Multiarm, Open-label, Multicenter, Phase 1b/2 Study to Evaluate Novel Combination Therapies in Subjects With Previously Treated Advanced EGFRm NSCLC

Clinical Trial IDs

  • ORG STUDY ID: D6070C00004
  • NCT ID: NCT03381274

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
MEDI9447Arm A
OsimertinibArm A
AZD4635Arm B

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalMEDI9447 and osimertinib
  • MEDI9447
  • Osimertinib
Arm BExperimentalMEDI9447 and AZD4635
  • MEDI9447
  • AZD4635

Eligibility 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
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events as a measure of safety
Time Frame:Screening through 90 days after last dose of investigational product
Safety Issue:
Description:The primary endpoint is safety as assessed by the presence of adverse events and serious adverse events

Secondary Outcome Measures

Measure:Duration of Response (DoR)
Time Frame:During treatment through study completion, about 2 years after the last subject dosed
Safety Issue:
Description: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
Measure:Disease Control (DC)
Time Frame:During treatment through study completion, about 2 years after the last subject dosed
Safety Issue:
Description:Defined as complete response (CR), partial response (PR) or stable disease (SD)
Measure:Progression Free Survival (PFS)
Time Frame:During treatment through study completion, about 2 years after the last subject dosed
Safety Issue:
Description:From the start of treatment with investigational product until the first documentation of disease progression or death due to any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:During treatment through study completion, about 2 years after the last subject dosed
Safety Issue:
Description:From the start of treatment with investigational product until death due to any cause
Measure:Objective Response by T790M status
Time Frame:During treatment through study completion, about 2 years after the last subject dosed
Safety Issue:
Description:Defined as best overall response of confirmed CR or confirmed PR according to RECIST version 1.1
Measure:Disease Control by T790M status
Time Frame:During treatment through study completion, about 2 years after the last subject dosed
Safety Issue:
Description:Defined as CR, PR or SD
Measure:Serum MEDI9447 concentration levels
Time Frame:During treatment through 90 days after last dose of investigational product
Safety Issue:
Description:Pharmacokinetic
Measure:Serum Osimertinib concentration levels
Time Frame:During treatment through 90 days after last dose of investigational product
Safety Issue:
Description:Pharmacokinetic
Measure:Serum AZD4635 concentration levels
Time Frame:During treatment through 90 days after last dose of investigational product
Safety Issue:
Description:Pharmacokinetic
Measure:Development of detectable anti-drug antibody(ADA) to MEDI9447
Time Frame:During treatment through 90 days after last dose of investigational product
Safety Issue:
Description:Immunogenicity

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MedImmune LLC

Trial Keywords

  • EGFR mutated, CD73, A2AR, oleclumab, MEDI9447, AZD4635, osimertinib, NSCLC, immunotherapy

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