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:

Recruiting

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
  • Non-small Cell Lung Cancer (Adenocarcinoma)

Interventions

DrugSynonymsArms
TMT212trametinibPDR001+trametinib in TNBC
EGF816PDR001+EGF816 in TNBC

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.

Detailed Description

Trial Arms

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

                    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.

                    - 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

                    - 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.

                    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:Recruiting
                    Lead Sponsor:Novartis Pharmaceuticals

                    Trial Keywords

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

                    Last Updated

                    February 22, 2017