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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 )

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma Biological: PDR001 Biological: ACZ885 Biological: CJM112 Drug: TMT212 Drug: EGF816 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 432 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 23, 2016
Estimated Primary Completion Date : May 18, 2020
Estimated Study Completion Date : May 19, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PDR001+canakinumab in TNBC Biological: PDR001
Powder for solution for infusion

Biological: ACZ885
Solution for injection
Other Name: canakinumab

Experimental: PDR001+CJM112 in TNBC Biological: PDR001
Powder for solution for infusion

Biological: CJM112
Solution for infusion

Experimental: PDR001+trametinib in TNBC Biological: PDR001
Powder for solution for infusion

Drug: TMT212
Tablets
Other Name: trametinib

Experimental: PDR001+EGF816 in TNBC Biological: PDR001
Powder for solution for infusion

Drug: EGF816
Tablets

Experimental: PDR001+canakinumab in NSCLC Biological: PDR001
Powder for solution for infusion

Biological: ACZ885
Solution for injection
Other Name: canakinumab

Experimental: PDR001+CJM112 in NSCLC Biological: PDR001
Powder for solution for infusion

Biological: CJM112
Solution for infusion

Experimental: PDR001+ trametinib in NSCLC Biological: PDR001
Powder for solution for infusion

Drug: TMT212
Tablets
Other Name: trametinib

Experimental: PDR001+EGF816 in NSCLC Biological: PDR001
Powder for solution for infusion

Drug: EGF816
Tablets

Experimental: PDR001+canakinumab in CRC Biological: PDR001
Powder for solution for infusion

Biological: ACZ885
Solution for injection
Other Name: canakinumab

Experimental: PDR001+ CJM112 in CRC Biological: PDR001
Powder for solution for infusion

Biological: CJM112
Solution for infusion

Experimental: PDR001+trametinib in CRC Biological: PDR001
Powder for solution for infusion

Drug: TMT212
Tablets
Other Name: trametinib

Experimental: PDR001+ EGF816 in CRC Biological: PDR001
Powder for solution for infusion

Drug: EGF816
Tablets

Experimental: canakinumab in TNBC Biological: ACZ885
Solution for injection
Other Name: canakinumab

Experimental: canakinumab in NSCLC Biological: ACZ885
Solution for injection
Other Name: canakinumab

Experimental: canakinumab in CRC Biological: ACZ885
Solution for injection
Other Name: canakinumab




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only) [ Time Frame: During the first two cycles; Cycle = 28 days ]
  4. Frequency of dose interruptions [ Time Frame: Throughout the study at every visit, an average of 1 year ]
  5. Dose intensities [ Time Frame: Throughout the study at every visit, an average of 1 year ]
  6. 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 ]
  7. Frequency of dose reductions [ Time Frame: Throughout the study at every visit, an average of 1 year ]

Secondary Outcome Measures :
  1. 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 ]
  2. Changes from baseline in electrocardiogram (ECG) parameters [ Time Frame: Baseline and end of treatment, an average of 1 year ]
  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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 ]
  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


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): NCT02900664


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Maryland
Novartis Investigative Site Recruiting
Baltimore, Maryland, United States, 21287-0013
United States, Massachusetts
Novartis Investigative Site Recruiting
Boston, Massachusetts, United States, 02215
United States, Tennessee
Novartis Investigative Site Recruiting
Nashville, Tennessee, United States, 37203
Contact: Michael Cain    615-329-7417    Michael.Cain@sarahcannon.com   
Principal Investigator: Melissa Johnson         
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Contact: Munir Yi Chowdury    713-563-9033    MChowdhury@mdanderson.org   
Principal Investigator: Siqing Fu         
Belgium
Novartis Investigative Site Recruiting
Brussels, Belgium, BE-B-1200
Novartis Investigative Site Recruiting
Wilrijk, Belgium, 2610
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Novartis Investigative Site Recruiting
Montreal, Quebec, Canada, H3T 1E2
France
Novartis Investigative Site Recruiting
Lyon Cedex, France, 69373
Novartis Investigative Site Recruiting
Paris, France, 75231
Novartis Investigative Site Recruiting
Toulouse Cedex 9, France, 31059
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Israel
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 6423906
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20132
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 119228
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site Recruiting
Madrid, Spain, 28009
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Taiwan
Novartis Investigative Site Recruiting
Tainan, Taiwan, 70403
Novartis Investigative Site Recruiting
Taoyuan, Taiwan, 33305
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02900664     History of Changes
Other Study ID Numbers: CPDR001X2103
2016-000633-49 ( EudraCT Number )
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
CRC
TNBC
NSCLC (adenocarcinoma)
Immunomodulation
Biomarkers
Bayesian logistic regression model
PDR001
Immunotherapy

Additional relevant MeSH terms:
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Colorectal Neoplasms
Adenocarcinoma
Triple Negative Breast Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Breast Neoplasms
Breast Diseases
Skin Diseases
Trametinib
(R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo(d)imidazol-2-yl)-2-methylisonicotinamide
Antibodies, Monoclonal
Nicotine
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Ganglionic Stimulants