Clinical Trials /

Phase 2 Study of MPDL3280A Combined With CDX-1401 in NY-ESO 1 (+) IIIB, IV or Recurrent Non-Small Cell Lung Cancer

NCT02495636

Description:

The primary purpose of this study is to look at effects, good or bad, of combining two investigational anti-cancer drugs called MPDL3280A and CDX-1401. CDX-1401 is given in combination with a third agent, poly-ICLC, which is another investigational drug that is believed to work together with CDX-1401. All investigational drugs, MPDL3280A and CDX-1401 in conjunction with poly-ICLC, have been evaluated separately in prior studies; however, this is the first study assessing the combination therapy.

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

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Phase 2 Study of <span class="go-doc-concept go-doc-intervention">MPDL3280A</span> Combined With CDX-1401 in NY-ESO 1 (+) IIIB, IV or Recurrent Non-Small Cell Lung Cancer

Title

  • Brief Title: Phase 2 Study of MPDL3280A Combined With CDX-1401 in NY-ESO 1 (+) IIIB, IV or Recurrent Non-Small Cell Lung Cancer
  • Official Title: Phase 2 Study of MPDL3280A Combined With CDX-1401 in NY-ESO 1 (+) IIIB, IV or Recurrent Non-Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02495636

    ORG ID: 1501015233

    Trial Conditions

    Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    CDX-1401 Safety Run Up Group, Expanded Trial Group
    MPDL3280A Safety Run Up Group, Expanded Trial Group

    Trial Purpose

    The primary purpose of this study is to look at effects, good or bad, of combining two
    investigational anti-cancer drugs called MPDL3280A and CDX-1401. CDX-1401 is given in
    combination with a third agent, poly-ICLC, which is another investigational drug that is
    believed to work together with CDX-1401. All investigational drugs, MPDL3280A and CDX-1401
    in conjunction with poly-ICLC, have been evaluated separately in prior studies; however,
    this is the first study assessing the combination therapy.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Safety Run Up Group Experimental The first 12 patients to be enrolled will initiate therapy with CDX-1401 alone, with the addition of MPDL3280A the day of their 4th CDX-1401 vaccination (week 7). These patients will undergo a tumor biopsy prior to initiation of trial therapy, after their 3rd CDX-1401 vaccination (during week 6) and after their 3rd MPDL3280A infusion (during week 14 or 15, if there are no dose delays). Although we don't expect significant synergistic toxicities of combination therapy based on mechanism of action/ formulation/ administration/ distribution of CDX-1401 and past vaccine/ immune checkpoint trials, these first 12 patients will constitute a safety run in group. CDX-1401, MPDL3280A
    Expanded Trial Group Experimental If there are no unexpected toxicities (no more than 3 of 12 patients with grade 3+ treatment related events as defined in 4.1.1), an additional 28 patients will be enrolled. Unlike the first 12 patients, these additional 28 patients will initiate both CDX-1401 and MPDL3280A on the same day, and will undergo tumor biopsies before starting trial therapy and after their 3rd CDX-1401 vaccination (during week 6). CDX-1401, MPDL3280A

    Eligibility Criteria

    Inclusion Criteria:

    A. Signed Informed Consent B. Ability to comply with the protocol C. Age 18 years D.
    Histologically or cytologically documented, locally advanced or metastatic (i.e., Stage
    IIIB not eligible for definitive chemoradiotherapy, Stage IV, or recurrent) NSCLC (per the
    American Joint Committee /AJCC staging system) E. Measurable disease, as defined by RECIST
    v1.1. Previously irradiated lesions can be counted as target lesions if clearly
    progressing after radiation.

    F. Chemotherapy naive and treated patients will be eligible, with no limit on number of
    prior therapies. Patients with NSCLC known to harbor an ALK rearrangement, or EGFR
    mutation known to be sensitive to FDA approved tyrosine kinase inhibitors (TKI), are only
    eligible after experiencing disease progression (during or after treatment) or intolerance
    to an FDA approved EGFR TKI or ALK TKI, respectively.

    G. Positive NY-ESO-1 expression by RT-PCR and/or IHC will be required for entry, as
    determined by analysis at the trial central laboratory.

    H. At least one tumor amenable to excisional, core or forceps (transbronchial) biopsy.
    Patients must be willing to undergo tumor biopsies before starting therapy and after the
    3rd CDX-1401 injection. Additionally, the first 12 patients enrolled must consent to a
    third tumor biopsy to be performed after the 3rd MPDL3280A infusion.

    I. ECOG performance status of 0 to 2 J. For female patients of childbearing potential and
    male patients with partners of childbearing potential, agreement (by patient and/or
    partner) to use a highly effective form(s) of contraception (i.e., one that results in a
    low failure rate [<1% per year] when used consistently and correctly) and to continue its
    use for 6 months after the last dose of trial therapy. Highly effective contraception is
    one with a failure rate of <0.1%. Birth control pills on their own do not achieve that
    rate.

    K. Adequate hematologic and end-organ function, defined by the following laboratory
    results obtained within 14 days prior to the first study treatment:

    - ANC 1500 cells/L (without granulocyte colony-stimulating factor support within 2
    weeks prior to Cycle 1, Day 1)

    - Platelet count 100,000/L (without transfusion within 2 weeks prior to Cycle 1, Day
    1)

    - Hemoglobin 9.0 g/dL (Patients may be transfused to meet this criterion)

    - AST, ALT, and ALP 2.5 xULN, with the following exceptions: Patients with documented
    liver metastases: AST and/or ALT5 x ULN; Patients with documented liver or bone
    metastases: ALP 5 x ULN

    - Serum bilirubin 1.5 xULN (Patients with known Gilbert disease who have serum
    bilirubin level 3 xULN may be enrolled)

    - INR and aPTT1.5 x ULN (This applies only to patients who are not receiving
    therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be
    on a stable dose)

    - Serum creatinine 1.5 xULN or creatinine clearance 50 mL/min

    Exclusion Criteria:

    A. Has an active autoimmune disease requiring systemic treatment within the past 3 months
    or a documented history of clinically severe autoimmune disease, or a syndrome that
    requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved
    childhood asthma/atopy would be an exception to this rule. Subjects who require
    intermittent use of inhaled steroids or local steroid injections would not be excluded
    from the study. Subjects with hypothyroidism stable on hormone replacement, or psoriasis
    not requiring systemic therapy (within the past 3 years) will not be excluded from the
    study.

    B. Generalized dermatologic conditions (such as allergic reactions, infection, edema, or
    scarring) that will not allow for study drug administration at a site of normal skin or
    evaluation of localized adverse events.

    C. Symptomatic or untreated CNS metastases. Patients with a history of treated
    asymptomatic CNS metastases are eligible, provided they meet all of the following
    criteria: No evidence of interim progression between the completion of CNS-directed
    therapy and the start of trial therapy. No ongoing requirement for dexamethasone as
    therapy for CNS disease; anticonvulsants at a stable dose are allowed. Completed
    stereotactic radiation at least 1 week prior to Cycle 1, Day 1 or whole-brain radiation at
    least 2 weeks prior to Cycle 1, Day 1 D. Treatment with systemic immunosuppressive
    medications (including but not limited to, prednisone at doses > 10 mg (or equivalent dose
    of other corticosteroids), cyclophosphamide, tacrolimus, sirolimus, azathioprine,
    methotrexate, thalidomide, and antitumor necrosis factor [anti-TNF] agents) within 2 weeks
    prior to CDX-1401 administration (Inhaled or topically applied steroids, and acute and
    chronic standard-dose NSAIDs are permitted. Replacement steroids are also permitted).

    E. Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3
    weeks prior to initiation of study treatment; the following exceptions are allowed:

    - Hormone-replacement therapy or oral contraceptives

    - TKIs approved for treatment of NSCLC discontinued > 7 days prior to Cycle 1, Day 1.
    The baseline scan must be obtained after discontinuation of prior TKIs.

    F. Treatment with any other investigational agent or participation in another clinical
    trial with therapeutic intent within 28 days prior to enrollment; the following exceptions
    are allowed:

    - Unapproved/ experimental TKIs discontinued 14 days prior to Cycle 1, Day 1 G. Known
    infection with HIV, HBV or HCV. Patients with prior exposure to hepatitis, but no evidence
    of active or chronic infection, may be eligible.

    H. Active systemic infection requiring systemic antibiotic treatment within 72 hours prior
    to first dose of study treatment I. Uncontrolled intercurrent illness including, but not
    limited to, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric
    illness/social situations that would limit compliance with study requirements J. Women who
    are pregnant or lactating. K. Any underlying medical condition that in the Principal
    Investigator's opinion will make the administration of study drug hazardous to the patient
    or would obscure the interpretation of adverse events.

    L. Previous administration of vaccine therapy targeting NY-ESO-1 M. Prior treatment with
    immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, and anti-PD-L1
    therapeutic antibodies

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective Response Rate

    Secondary Outcome Measures

    Trial Keywords