Clinical Trials /

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

NCT02900664

Description:

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.

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

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: CPDR001X2103
  • SECONDARY ID: 2016-000633-49
  • NCT ID: NCT02900664

Conditions

  • Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma

Interventions

DrugSynonymsArms
PDR001PDR001+ CJM112 in CRC
ACZ885canakinumabPDR001+canakinumab in CRC
CJM112PDR001+ CJM112 in CRC
TMT212trametinibPDR001+ trametinib in NSCLC
EGF816PDR001+ EGF816 in CRC

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PDR001+canakinumab in TNBCExperimental
  • PDR001
  • ACZ885
PDR001+CJM112 in TNBCExperimental
  • PDR001
  • CJM112
PDR001+trametinib in TNBCExperimental
  • PDR001
  • TMT212
PDR001+EGF816 in TNBCExperimental
  • PDR001
  • EGF816
PDR001+canakinumab in NSCLCExperimental
  • PDR001
  • ACZ885
PDR001+CJM112 in NSCLCExperimental
  • PDR001
  • CJM112
PDR001+ trametinib in NSCLCExperimental
  • PDR001
  • TMT212
PDR001+EGF816 in NSCLCExperimental
  • PDR001
  • EGF816
PDR001+canakinumab in CRCExperimental
  • PDR001
  • ACZ885
PDR001+ CJM112 in CRCExperimental
  • PDR001
  • CJM112
PDR001+trametinib in CRCExperimental
  • PDR001
  • TMT212
PDR001+ EGF816 in CRCExperimental
  • PDR001
  • EGF816
canakinumab in TNBCExperimental
  • ACZ885
canakinumab in NSCLCExperimental
  • ACZ885
canakinumab in CRCExperimental
  • ACZ885

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:Changes from baseline in electrocardiogram (ECG) parameters
Time Frame:Baseline and end of treatment, an average of 1 year
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure: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
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure: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
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure: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)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure:Serum concentration of PDR001, canakinumab, CJM112
Time Frame:Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure:Plasma concentrations of trametinib and EGF816
Time Frame:Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure: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
Safety Issue:
Description:
Measure:PK parameters (Eg. TMax) of EGF816
Time Frame:Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure:PK parameters (Eg. TMax) of trametinib
Time Frame:Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure:PK parameter (Eg. TMax) of PDR001
Time Frame:Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure:PK parameters (Eg. TMax) of canakinumab
Time Frame:Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure:PK parameters (Eg. TMax) of CJM112
Time Frame:Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure: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)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Measure: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)
Safety Issue:
Description:T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • CRC
  • TNBC
  • NSCLC (adenocarcinoma)
  • Immunomodulation
  • Biomarkers
  • Bayesian logistic regression model
  • PDR001
  • Immunotherapy

Last Updated

April 28, 2021