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

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)

ClinicalTrials.gov Identifier: NCT02900664

Novartis Reference Number: CPDR001X2103

See if you pre-qualify

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study 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.

Condition 
Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma
Phase 
Phase 1
Overall status 
Active, not recruiting
Enrollment count 
290 participants
Start date 
Aug 23, 2016
Completion date 
Nov 04, 2020
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Biological
PDR001
Powder for solution for infusion
Biological
ACZ885
Solution for injection
Biological
CJM112
Solution for infusion
Drug
TMT212
Tablets
Drug
EGF816
Tablets

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.

Study Locations

United States
Sidney Kimmel Comprehensive Cancer Center SC-3
-
Baltimore, 21287-0013
Maryland
United States
Dana Farber Cancer Center
-
Boston, 02215
Massachusetts
United States
Sarah Cannon Research Institute
-
Nashville, 37203
Tennessee
United States
University of Texas MD Anderson Cancer Center
-
Houston, 77030
Texas
United States
Belgium
Novartis Investigative Site
-
Brussels, BE-B-1200
-
Belgium
Novartis Investigative Site
-
Wilrijk, 2610
-
Belgium
Canada
Novartis Investigative Site
-
Toronto, M5G 2M9
Ontario
Canada
Novartis Investigative Site
-
Montreal, H3T 1E2
Quebec
Canada
France
Novartis Investigative Site
-
Lyon Cedex, 69373
-
France
Novartis Investigative Site
-
Paris, 75231
-
France
Novartis Investigative Site
-
Toulouse Cedex 9, 31059
-
France
Novartis Investigative Site
-
Villejuif Cedex, 94800
-
France
Israel
Novartis Investigative Site
-
Tel Aviv, 6423906
-
Israel
Italy
Novartis Investigative Site
-
Milano, 20132
MI
Italy
Novartis Investigative Site
-
Rozzano, 20089
MI
Italy
Singapore
Novartis Investigative Site
-
Singapore, 119228
-
Singapore
Novartis Investigative Site
-
Singapore, 169610
-
Singapore
Spain
Novartis Investigative Site
-
Barcelona, 08036
Catalunya
Spain
Novartis Investigative Site
-
Hospitalet de LLobregat, 08907
Catalunya
Spain
Novartis Investigative Site
-
Madrid, 28009
-
Spain
Novartis Investigative Site
-
Madrid, 28050
-
Spain
Taiwan
Novartis Investigative Site
-
Tainan, 70403
-
Taiwan
Novartis Investigative Site
-
Taoyuan, 33305
-
Taiwan

Have a question?

Call 1-999-669-6682 or email [email protected]