Clinical Trials /

Phase I/II Study of PDR001 in Patients With Advanced Malignancies

NCT02404441

Description:

The purpose of this "first-in-human" study of PDR001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors. By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells. This study has been designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part. PDR001 will be administered every 2 weeks until patient experiences unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment is discontinued at the discretion of the investigator or the patient.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Phase I/II Study of <span class="go-doc-concept go-doc-intervention">PDR001</span> in Patients With Advanced Malignancies

Title

  • Brief Title: Phase I/II Study of PDR001 in Patients With Advanced Malignancies
  • Official Title: Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies
  • Clinical Trial IDs

    NCT ID: NCT02404441

    ORG ID: CPDR001X2101

    NCI ID: 2014-003929-17

    Trial Conditions

    Melanoma

    NSCLC

    Triple Negative Breast Cancer

    Other Solid Tumors

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    The purpose of this "first-in-human" study of PDR001 is to characterize the safety,
    tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001
    administered i.v. as a single agent to adult patients with solid tumors.

    By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits
    the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by
    activating effector T-cells and inhibiting regulatory T-cells.

    This study has been designed as a phase I/II, multi-center, open-label study starting with a
    phase I dose escalation part followed by a phase II part.

    PDR001 will be administered every 2 weeks until patient experiences unacceptable toxicity,
    progressive disease per immune related Response Criteria (irRC) and/or treatment is
    discontinued at the discretion of the investigator or the patient.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    patients with solid tumors Other Phase I Dose escalation cohorts
    Selected tumor types Other Phase II expansion: Selected tumor types: melanoma, NSCLC, triple negative breast cancer

    Eligibility Criteria

    Inclusion Criteria:

    - Written informed consent must be obtained prior to any screening procedures

    - Phase I part: Patients with advanced/metastatic solid tumors, with measurable or
    non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who
    have progressed despite standard therapy or are intolerant of standard therapy, or
    for whom no standard therapy exists.

    - Phase II part: Patients with advanced/metastatic solid tumors, with at least one
    measurable lesion as determined by RECIST version 1.1, who have received standard
    therapy (with the exception of PD-1- and PD-L1-directed therapies) or are intolerant
    of standard therapy, have progressed following their last prior therapy, and fit into
    one of the following groups:

    - Group 1: NSCLC:

    Patients with NSCLC must have had disease recurrence or progression during or after one
    prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease.
    Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab).

    Patients must have been tested for mutations affecting EGFR and ALK. Patients with a known
    mutation in one gene need not be tested for the other. Patients with ALK or EGFR-positive
    NSCLC must have had recurrent or progressive disease after treatment with the
    corresponding inhibitor and platinum doublet-based chemotherapy, in any sequence.

    - Group 2: Melanoma:

    Patients with melanoma must have clinical or radiological evidence of disease progression
    during or after:

    - For patient with BRAF wild type disease, at least one cycle of systemic treatment for
    advanced melanoma.

    - For patients with BRAF V600 mutation positive disease, treatment with a BRAF
    inhibitor (alone or in combination with other agents) and at least one other systemic
    treatment.

    - Group 3: Triple negatice breast cancer.

    - ECOG Performance Status 2.

    - Patients must have a site of disease amenable to biopsy, and be a candidate for
    tumor biopsy. Patient must be willing to undergo a new tumor biopsy at baseline,
    and during therapy on this study. For patients in the phase II part of the
    study, exceptions may be granted after documented discussion with Novartis.
    After a sufficient number of paired biopsies are collected, the decision may be
    taken to stop the collection of biopsies.

    Exclusion Criteria:

    - History of severe hypersensitivity reactions to other mAbs

    - Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
    type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
    requiring hormone replacement, psoriasis not requiring systemic treatment, or
    conditions not expected to recur in the absence of an external trigger are permitted
    to enroll.

    - Active infection requiring systemic antibiotic therapy.

    - HIV infection.

    - Active HBV or HCV infection.

    - Patients with ocular melanoma.

    - Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For
    cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas,
    4 weeks washout period. For patients receiving anticancer immunotherapies such as
    CTLA-4 antagonists, 6 weeks is indicated as the washout period.

    - Prior PD-1- or PD-L1-directed therapy.

    - Patients requiring chronic treatment with systemic steroid therapy, other than
    replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled,
    nasal and ophthalmic steroids are not prohibited.

    - Patients receiving systemic treatment with any immunosuppressive medication (other
    than steroids as described above).

    - Use of any vaccines against infectious diseases (e.g. influenza, varicella,
    pneumococcus) within 4 weeks of initiation of study treatment.

    - Presence of CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and
    ototoxicity, which are excluded if CTCAE grade 3) due to prior cancer therapy

    Other protocol defined Inclusion/Exclusion may apply.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Part l: The exposure (AUC(0-336h)) after first dose of treatment

    Part l: Incidence of dose limiting toxicities (DLTs)

    Part ll: Overall response Rate (ORR)

    Secondary Outcome Measures

    Safety and Tolerability as assessed by incidence and severity of adverse events, dose interruptions, reductions and dose intensity

    Presence and/or concentration of anti-PDR001

    Overall Response Rate (ORR) - Phase l only

    Progression Free Survival (PFS) - Phase l/ll

    Duration of Response (DOR) - Phase l/ll

    Disease Control Rate (DCR) - Phase l/ll

    Overall Response Rate (ORR) per immune related Response Criteria - Phase ll only

    Composite Serum pharmacokinetics (PK) parameters

    Serum concentration vs. time profiles

    Trial Keywords

    Phase I/II, PDR001, Checkpoint inhibitor, PD-1, PD-L1