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A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)

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ClinicalTrials.gov Identifier: NCT02900664
Recruitment Status : Recruiting
First Posted : September 14, 2016
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 17, 2016
First Posted Date  ICMJE September 14, 2016
Last Update Posted Date April 10, 2019
Actual Study Start Date  ICMJE August 23, 2016
Estimated Primary Completion Date May 18, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2016)
  • Frequency of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety [ Time Frame: Throughout the study at every visit, an average of 1 year ]
  • Changes between baseline and post-baseline laboratory parameters and vital signs. [ Time Frame: Baseline and throughout the study at every visit, an average of 1 year ]
  • Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only) [ Time Frame: During the first two cycles; Cycle = 28 days ]
  • Frequency of dose interruptions [ Time Frame: Throughout the study at every visit, an average of 1 year ]
  • Dose intensities [ Time Frame: Throughout the study at every visit, an average of 1 year ]
  • Severity of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety [ Time Frame: Throughout the study at every visit, an average of 1 year ]
  • Frequency of dose reductions [ Time Frame: Throughout the study at every visit, an average of 1 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02900664 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2016)
  • Key secondary: Histopathology of tumor infiltrating lymphocytes (TILs) [ Time Frame: Baseline and approximately after 2 cycles of treatment and at disease progression; Cycle = 28 days ]
  • Changes from baseline in electrocardiogram (ECG) parameters [ Time Frame: Baseline and end of treatment, an average of 1 year ]
  • Best overall response (BOR) [ Time Frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • Progression free survival (PFS) per irRC and RECIST v1.1 [ Time Frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • Treatment Free Survival (TFS) [ Time Frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • Presence and/or concentration of anti-PDR001 antibodies. [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • Serum concentration of PDR001, canakinumab, CJM112 [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • Plasma concentrations of trametinib and EGF816 [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • Key secondary: Histopathology of myeloid cell infiltrate by IHC (such as CD8, FoxP3 and myeloid markers as appropriate). [ Time Frame: Baseline and approximately after 3 cycles of treatment and at disease progression; cycle = 28 days ]
  • PK parameters (Eg. TMax) of EGF816 [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • PK parameters (Eg. TMax) of trametinib [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • PK parameter (Eg. TMax) of PDR001 [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • PK parameters (Eg. TMax) of canakinumab [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • PK parameters (Eg. TMax) of CJM112 [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • Presence and/or concentration of anti-canakinumab antibodies. [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
  • Presence and/or concentration of anti-CJM112 antibodies. [ Time Frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year) ]
    T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
Official Title  ICMJE Phase Ib, Open-label, Multi-center Study to Characterize the Safety, Tolerability and Pharmacodynamics (PD) of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
Brief Summary The purpose of this study is to combine the PDR001 checkpoint inhibitor with each of four agents with immunomodulatory activity to identify the doses and schedule for combination therapy and to preliminarily assess the safety, tolerability, pharmacological and clinical activity of these combinations.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma
Intervention  ICMJE
  • Biological: PDR001
    Powder for solution for infusion
  • Biological: ACZ885
    Solution for injection
    Other Name: canakinumab
  • Biological: CJM112
    Solution for infusion
  • Drug: TMT212
    Tablets
    Other Name: trametinib
  • Drug: EGF816
    Tablets
Study Arms  ICMJE
  • Experimental: PDR001+canakinumab in TNBC
    Interventions:
    • Biological: PDR001
    • Biological: ACZ885
  • Experimental: PDR001+CJM112 in TNBC
    Interventions:
    • Biological: PDR001
    • Biological: CJM112
  • Experimental: PDR001+trametinib in TNBC
    Interventions:
    • Biological: PDR001
    • Drug: TMT212
  • Experimental: PDR001+EGF816 in TNBC
    Interventions:
    • Biological: PDR001
    • Drug: EGF816
  • Experimental: PDR001+canakinumab in NSCLC
    Interventions:
    • Biological: PDR001
    • Biological: ACZ885
  • Experimental: PDR001+CJM112 in NSCLC
    Interventions:
    • Biological: PDR001
    • Biological: CJM112
  • Experimental: PDR001+ trametinib in NSCLC
    Interventions:
    • Biological: PDR001
    • Drug: TMT212
  • Experimental: PDR001+EGF816 in NSCLC
    Interventions:
    • Biological: PDR001
    • Drug: EGF816
  • Experimental: PDR001+canakinumab in CRC
    Interventions:
    • Biological: PDR001
    • Biological: ACZ885
  • Experimental: PDR001+ CJM112 in CRC
    Interventions:
    • Biological: PDR001
    • Biological: CJM112
  • Experimental: PDR001+trametinib in CRC
    Interventions:
    • Biological: PDR001
    • Drug: TMT212
  • Experimental: PDR001+ EGF816 in CRC
    Interventions:
    • Biological: PDR001
    • Drug: EGF816
  • Experimental: canakinumab in TNBC
    Intervention: Biological: ACZ885
  • Experimental: canakinumab in NSCLC
    Intervention: Biological: ACZ885
  • Experimental: canakinumab in CRC
    Intervention: Biological: ACZ885
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2016)
432
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 19, 2020
Estimated Primary Completion Date May 18, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to standard therapy, and for whom no effective therapy is available.

Patients must fit into one of the following groups:

  • Colorectal cancer (CRC) (not mismatch repair deficient by local assay including PCR and/or immunohistochemistry)
  • Non-small cell lung cancer (NSCLC) (adenocarcinoma)
  • Triple Negative Breast Cancer (TNBC) (D
  • ECOG Performance Status ≤ 2
  • Patient must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at baseline, and again during therapy on this study.
  • Prior therapy with PD-1/PDL-1 inhibitors is allowed provided any toxicity attributed to prior PD-1- or PD-L1-directed therapy did not lead to discontinuation of therapy.
  • Written informed consent must be obtained prior to any screening procedures other than procedures performed as part of standard of care.

Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

  • Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks.
  • History of severe hypersensitivity reactions to other monoclonal antibodies.
  • Out of range laboratory values for measures of hepatic and renal function, electrolytes and blood counts
  • Impaired cardiac function or clinically significant cardiac disease.
  • Patients with active, known or suspected autoimmune disease.
  • Human Immunodeficiency Virus infection at screening.
  • Escalation part: Active Hepatitis B (HBV) or Hepatitis C (HCV) virus infection at screening.

Expansion part: Patients with active HBV or HCV are excluded, excepting those patients undergoing treatment for HBV or HCV.

  • Malignant disease, other than that being treated in this study.
  • Recent systemic anti-cancer therapy
  • Active infection requiring systemic antibiotic therapy.
  • Patients requiring chronic treatment with systemic steroid therapy, other than replacement dose steroids in the setting of adrenal insufficiency or treatment with low, stable dose of steroid (<10mg/ day prednisone or equivalent) for stable CNS metastatic disease.
  • Patients receiving systemic treatment with any immunosuppressive medication, excepting the above
  • Use of any live vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
  • Participation in an interventional, investigational study within 2 weeks of the first dose of study treatment.
  • Presence of ≥ CTCAE grade 2 toxicity (except alopecia and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy.
  • Recent use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF)

Additional exclusion criteria for Combination arm PDR001+canakinumab and single-agent canakinumab

  • Patients with tuberculosis (TB). Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
  • Patients who have been infected with HBV or HCV including those with inactive disease.

Additional exclusion criteria for Combination arm PDR001+CJM112

  • Patients with TB. Note: Patient with latent TB may be eligible based on the investigator's benefit-risk assessment.
  • Patients with history of and/or active inflammatory bowel disease.
  • Active skin or soft tissue infection including cellulitis, erysipelas, impetigo, furuncle,carbuncle, abscess, or fasciitis.
  • Active candida infection, including mucocutaneous infection or history of invasive candidiasis.

Additional exclusion criteria for Combination arm PDR001+trametinib

  • Patients with history of retinal vein oclusion.
  • Patients with history of interstitial lung disease or pneumonitis.
  • Patients with cardiomyopathy and/or LVEF < LLN.
  • Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners.
  • Hemoglobin (Hgb) < 9 g/dL without growth factor or transfusion support
  • Women of child-bearing potential using hormonal contraception, unless an additional contraception method is also used according to the Mekinist® label.

Additional exclusion criteria for Combination arm PDR001+EGF816

  • NSCLC patients with EGFR mutant tumors.
  • Strong inhibitors and strong inducers of CYP3A4 should not be used concomitantly.
  • Patients with history of interstitial lung disease.
  • Patients who have been infected with HBV or HCV including those with inactive disease.
  • Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of oral combination partners
  • Patients cannot have received radiotherapy to lung fields within 6 months of study treatment start.

Other protocol-defined exclusion criteria may apply.

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: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Israel,   Italy,   Singapore,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02900664
Other Study ID Numbers  ICMJE CPDR001X2103
2016-000633-49 ( 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: No
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 April 2019

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