Clinical Trials /

Phase 1/2 Study of Ensartinib and Durvalumab, in ALK-rearranged Non-small Cell Lung Cancer

NCT02898116

Description:

This was a Phase 1/2, open-label, multicenter, single-arm study of combination therapy with ensartinib, an anaplastic lymphoma kinase (ALK) inhibitor, and durvalumab, an anti-programmed cell death ligand 1 (PD-L1) antibody, in subjects with ALK-rearranged (ALK-positive) non-small cell lung cancer (NSCLC). Primary study objectives were to determine the recommended combination dose (RCD) and safety and tolerability of the combination. Further objectives were to evaluate the clinical efficacy and biologic activity of the combination.

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

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title:A Study of ALK Inhibitor, Ensartinib, and Anti-PD-L1, Durvalumab, in Subjects With ALK-rearranged Non-small Cell Lung Cancer
  • Official Title:A Phase 1/2 Study of ALK Inhibitor, Ensartinib (X-396), and Anti-PD-L1, Durvalumab (MEDI4736), in Subjects With ALK-rearranged (ALK-positive) Non-small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: LUD2014-012-ALK
  • NCT ID: NCT02898116

Trial Conditions

  • Non-small Cell Lung Cancer
  • Carcinoma
  • NSCLC

Trial Interventions

DrugSynonymsArms
EnsartinibX-396Esartinib monotherapy
DurvalumabMEDI4736Combination Treatment

Trial Purpose

This is an open-label, multicenter, single-arm study to evaluate the safety and preliminary efficacy of a targeted therapy for NSCLC in combination with a checkpoint inhibitor:

- Ensartinib (X-396), an anaplastic lymphoma kinase (ALK) Inhibitor and

- Durvalumab (MEDI4736), an anti-programmed cell death ligand 1 (PD-L1) antibody.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Esartinib monotherapyExperimentalThere will be a run-in period where ensartinib will be given as monotherapy for 2 cycles. Subjects who do not qualify for combination treatment may continue on monotherapy.
  • Ensartinib
    Combination TreatmentExperimentalSubjects who qualify for combination treatment will receive ensartinib (X-396) by mouth daily and durvalumab (MEDI4736) intravenously every 4 weeks.
    • Ensartinib
    • Durvalumab

    Eligibility Criteria

    Inclusion Criteria:

    - Histologic confirmation of metastatic non-small cell lung cancer (NSCLC) and confirmed ALK rearrangement.

    - Measurable disease according to RECIST 1.1.

    - Availability of archival (diagnostic) specimens and willing to undergo a pre-treatment biopsy.

    - Subjects with treated brain metastases must have been treated with surgery and/or radiation therapy ≥ 21 days pre-study and must be clinically stable.

    - Laboratory parameters for vital functions should be in the normal range or not clinically significant.

    - Body weight > 30 kilograms.

    Exclusion Criteria:

    - Treatment with an investigational agent within 4 weeks of starting treatment.

    - Prior treatment with anti-PD-1, PD-L1, or CTLA4, or ensartinib (X-396).

    - Active, suspected or prior documented autoimmune disease.

    - Subjects with clinically significant cardiovascular disease.

    - History of pneumonitis or interstitial lung disease, or any unresolved immune-related adverse events.

    - Major surgery within 4 weeks of starting treatment.

    - Active infection including tuberculosis, hepatitis B or C, or human immunodeficiency virus.

    - History of allogenic organ transplant.

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of Adverse Events
    Time Frame:up to 17 months
    Safety Issue:Yes
    Description:Clinical laboratory tests, vital signs and weight measurements, physical exams, ECG, Eastern Cooperative Oncology Group (ECOG) performance status evaluation, imaging scans and any other medically indicated assessments, including subject interviews, will be performed to detect new abnormalities and deterioration of any preexisting conditions. The Investigator will evaluate any laboratory abnormalities for clinical significance, and clinically significant abnormalities will be recorded as adverse events. All treatment-emergent clinically significant abnormalities and deterioration from time of signing the informed consent to the end of study visit will be recorded in the Case Report Forms (CRFs) as adverse events and graded according to the CTCAE Version 4.03.

    Secondary Outcome Measures

    Measure:Progression Free Survival Rate
    Time Frame:up to 24 weeks
    Safety Issue:No
    Description:
    Measure:Response Rate
    Time Frame:up to 24 weeks
    Safety Issue:No
    Description:
    Measure:Overall Best Response
    Time Frame:up to 48 weeks
    Safety Issue:No
    Description:
    Measure:Disease Control Rate (DCR)
    Time Frame:up to 48 weeks
    Safety Issue:No
    Description:
    Measure:Duration of Response (DoR)
    Time Frame:up to 48 weeks
    Safety Issue:No
    Description:
    Measure:Progression Free Survival (PFS)
    Time Frame:up to 5 years
    Safety Issue:No
    Description:
    Measure:Overall Survival
    Time Frame:up to 5 years
    Safety Issue:No
    Description:

    Trial Keywords

    • ALK-rearranged
    • ALK-positive
    • ALK Inhibitor
    • Ensartinib
    • X-396
    • anti-PD-L1
    • Durvalumab
    • MEDI4736
    • ALK