Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT02404441
Recruitment Status : Active, not recruiting
First Posted : March 31, 2015
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Melanoma NSCLC Triple Negative Breast Cancer Anaplastic Thyroid Cancer Other Solid Tumors Biological: PDR001 Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 319 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies
Actual Study Start Date : April 27, 2015
Estimated Primary Completion Date : May 20, 2020
Estimated Study Completion Date : May 20, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
patients with solid tumors
Phase I Dose escalation cohorts
Biological: PDR001
anti-PD1 antibody

Selected tumor types
Phase II expansion: Selected tumor types: melanoma, NSCLC, triple negative breast cancer, anaplastic thyroid cancer
Biological: PDR001
anti-PD1 antibody




Primary Outcome Measures :
  1. Part l: The exposure (AUC(0-336h)) after first dose of treatment [ Time Frame: First 28 days of treatment ]
    To estimate the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001

  2. Part l: Incidence of dose limiting toxicities (DLTs) [ Time Frame: First 28 days of treatment ]
    To estimate the RP2D and/or the MTD for PDR001

  3. Part ll: Overall response Rate (ORR) [ Time Frame: when all patients have completed at least 6 cycles of treatment or discontinued treatment. An average of 1 year duration is expected. ]
    As per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - to estimte the anti-tumor activity of PDR001. Each cycle = 28 days


Secondary Outcome Measures :
  1. Safety and Tolerability as assessed by incidence and severity of adverse events, dose interruptions, reductions and dose intensity [ Time Frame: continuously during study until 30 days after post study treatment ]
    Safety as assessed by Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory parameters, vital signs and electrocardiograms (ECGs) Tolerability as assessed by dose interruptions, reductions and dose intensity

  2. Presence and/or concentration of anti-PDR001 [ Time Frame: Cycle 1 day 1; Cycle 2 day 1; Cycle 3 day 1; Cycle 4 day 1; Cycle 5 day 1; Cycle 6 day 1; End of Treatment. ]
    To assess emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment = expected to be in average 1 year after the start of study treatment

  3. Overall Response Rate (ORR) - Phase l only [ Time Frame: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected. ]
    Preliminary antitumor activity of PDR001

  4. Progression Free Survival (PFS) - Phase l/ll [ Time Frame: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected. ]
    Preliminary antitumor activity of PDR001

  5. Duration of Response (DOR) - Phase l/ll [ Time Frame: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected. ]
    Preliminary antitumor activity of PDR001

  6. Disease Control Rate (DCR) - Phase l/ll [ Time Frame: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected. ]
    Preliminary antitumor activity of PDR001

  7. Overall Response Rate (ORR) per immune related Response Criteria - Phase ll only [ Time Frame: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected. ]
    Preliminary antitumor activity of PDR001

  8. Composite Serum pharmacokinetics (PK) parameters [ Time Frame: cycles 1 days 1, 2, 3, 4, 8, 11, 15. Cycle 2 day 1. Cycle 3 days 1, 2, 3, 4, 8, 11, 15. Cycle 4 day 1, Cycle 5 day 1, Cycle 6 day 1, End of Treatment. ]
    e.g., AUC, Cmax, Tmax, half-life to characterize the pharmacokinetic profile of PDR001. End of treatment = expected to be in average 1 year after the start of study treatment

  9. Serum concentration vs. time profiles [ Time Frame: cycles 1 days 1, 2, 3, 4, 8, 11, 15. Cycle 2 day 1. Cycle 3 days 1, 2, 3, 4, 8, 11, 15. Cycle 4 day 1, Cycle 5 day 1, Cycle 6 day 1, End of Treatment. ]
    To characterize the pharmacokinetic profile of PDR001. End of treatment = expected to be in average 1 year after the start of study treatment



Information from the National Library of Medicine

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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 progressed following their last prior therapy, and fit into one of the following groups:

    • Group 1a and 1b: NSCLC:

Patients with NSCLC must have had disease recurrence or progression during or after no more than one prior systemic chemotherapy regimen (platinum doublet-based) for advanced or metastatic disease. Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab).

Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). All patients must be tested for EGFR mutational status and, for ALK translocation status if no mutation is detected in EGFR. Patients with ALK translocation-positive NSCLC must have had disease progression following treatment with a corresponding inhibitor and no more than one systemic chemotherapy regimen (platinum doublet-based), in any sequence.

  • Group 2: Melanoma:

All patients must have been tested for BRAF mutations. Patients with V600 mutation positive melanoma must have clinical or radiological evidence of disease progression during or after treatment with a BRAF inhibitor alone or in combination with other agents.

  • Group 3: Triple negatice breast cancer.
  • Group 4: Anaplastic thyroid cancer
  • Patients are not required to have received or progressed on a prior therapy.
  • Patients must not be at short term risk for life threatening complications (such as airway compromise or bleeding from locoregional or metastatic disease,).
  • Chemoradiation and/or surgery should be considered prior to study entry for those patients with locally advanced disease if those therapies are considered to be in the best interest of the patient.

    • ECOG Performance Status ≤ 1.
    • 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 or at molecular pre-screening if applicable, 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.


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): NCT02404441


  Show 43 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02404441     History of Changes
Other Study ID Numbers: CPDR001X2101
2014-003929-17 ( EudraCT Number )
First Posted: March 31, 2015    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Phase I/II, PDR001, Checkpoint inhibitor, PD-1, PD-L1

Additional relevant MeSH terms:
Layout table for MeSH terms
Thyroid Neoplasms
Triple Negative Breast Neoplasms
Thyroid Carcinoma, Anaplastic
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type