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

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ClinicalTrials.gov Identifier: NCT02404441
Recruitment Status : Completed
First Posted : March 31, 2015
Results First Posted : September 29, 2021
Last Update Posted : September 29, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 20, 2015
First Posted Date  ICMJE March 31, 2015
Results First Submitted Date  ICMJE July 21, 2021
Results First Posted Date  ICMJE September 29, 2021
Last Update Posted Date September 29, 2021
Actual Study Start Date  ICMJE April 27, 2015
Actual Primary Completion Date July 21, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2021)
  • Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) [ Time Frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3) ]
    Estimated the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001. AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.
  • Phase l: Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 8 months ]
    DLT is defined as an adverse event (AE) or abnormal laboratory value of common terminology criteria for adverse events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first cycle of treatment with PDR001 during the dose escalation part of the study for which relationship to study treatment cannot be ruled out, with some exceptions.
  • Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) [ Time Frame: 61 months ]
    ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required. PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
  • 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
  • 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
  • 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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2021)
  • Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) [ Time Frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) ]
    AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
  • Phase I: Serum Pharmacokinetic (PK) Parameter Cmax [ Time Frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) ]
    The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
  • Phase I: Serum Pharmacokinetic (PK) Parameter Tmax [ Time Frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) ]
    The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
  • Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) [ Time Frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) ]
    AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
  • Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax [ Time Frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) ]
    The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
  • Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax [ Time Frame: Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) ]
    The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
  • Phase I: Presence and/or Concentration of Anti-PDR001 [ Time Frame: 42 months ]
    Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment.
  • Phase II: Presence and/or Concentration of Anti-PDR001 [ Time Frame: 42 months ]
    Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment. For Treatment -induced ADA-positive, Percentage was based on subjects ADA-negative at baseline. For Treatment-boosted ADA-positive, Percentage was based on subjects ADA-positive at baseline.
  • Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 [ Time Frame: 27 months ]
    ORR is the percentage of participants with a best overall response of complete response CR or partial response PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
  • Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 [ Time Frame: 27 months ]
    DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
  • Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 [ Time Frame: 27 months ]
    PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
  • Phase I: Duration of Response (DOR) as Per RECIST v1.1 [ Time Frame: 27 months ]
    DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required; PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required; PD =progression <= 12 weeks after randomization/start of treatment (and not qualifying for CR, PR or SD). SD = at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment
  • Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) [ Time Frame: 27 months ]
    ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
  • Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC [ Time Frame: 27 months ]
    DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
  • Phase l Only: Progression Free Survival (PFS) as Per irRC [ Time Frame: 27 months ]
    PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
  • Phase I: Duration of Response (DOR) as Per irRC [ Time Frame: 61 Days ]
    DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug
  • Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 [ Time Frame: 61 months ]
    DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
  • Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 [ Time Frame: 61 months ]
    PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
  • Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1 [ Time Frame: 61 months ]
    DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. PD = progression <= start of treatment (and not qualifying for CR, PR or SD). SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
  • Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC [ Time Frame: 61 months ]
    ORR is the percentage of participants with a best overall response CR or PR as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
  • Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC [ Time Frame: 61 months ]
    DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
  • Phase II: Progression Free Survival (PFS) Per irRC [ Time Frame: 61 months ]
    PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
  • Phase II: Duration of Response (DOR) Per irRC [ Time Frame: 61 months ]
    DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug
Original Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/II Study of PDR001 in Patients With Advanced Malignancies
Official Title  ICMJE Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies
Brief Summary

The purpose of this "first-in-human" study of PDR001 was 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.

Detailed Description

This study was 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.

Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Melanoma
  • Non-small Sell Lung Cancer (NSCLC)
  • Triple Negative Breast Cancer
  • Anaplastic Thyroid Cancer
  • Other Solid Tumors
Intervention  ICMJE Biological: PDR001
anti-PD1 antibody
Study Arms  ICMJE
  • patients with solid tumors
    Phase I Dose escalation cohorts
    Intervention: Biological: PDR001
  • Selected tumor types
    Phase II expansion: Selected tumor types: melanoma, NSCLC, triple negative breast cancer, anaplastic thyroid cancer
    Intervention: Biological: PDR001
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 22, 2018)
319
Original Estimated Enrollment  ICMJE
 (submitted: March 30, 2015)
180
Actual Study Completion Date  ICMJE July 21, 2020
Actual Primary Completion Date July 21, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent must have been 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Germany,   Hungary,   Italy,   Lebanon,   Netherlands,   Norway,   Poland,   Spain,   Taiwan,   Thailand,   Turkey,   United States
Removed Location Countries Japan
 
Administrative Information
NCT Number  ICMJE NCT02404441
Other Study ID Numbers  ICMJE CPDR001X2101
2014-003929-17 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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

URL: https://www.clinicalstudydatarequest.com
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP