A Study of PDR001 in Combination With CJM112, EGF816, Ilaris® (Canakinumab) or Mekinist® (Trametinib)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02900664 |
Recruitment Status :
Completed
First Posted : September 14, 2016
Last Update Posted : March 29, 2022
|
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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 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 283 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 |
Actual Primary Completion Date : | March 17, 2021 |
Actual Study Completion Date : | March 17, 2021 |
Arm | Intervention/treatment |
---|---|
Experimental: PDR + ACZ 100mg Q8W
PDR + ACZ 100mg Q8W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: ACZ885 Solution for injection
Other Name: canakinumab |
Experimental: PDR + ACZ 300mg Q8W
PDR + ACZ 300mg Q8W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: ACZ885 Solution for injection
Other Name: canakinumab |
Experimental: PDR + ACZ RDE TNBC
PDR + ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC)
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: ACZ885 Solution for injection
Other Name: canakinumab |
Experimental: PDR + ACZ RDE NSCLC
PDR + ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC)
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: ACZ885 Solution for injection
Other Name: canakinumab |
Experimental: PDR + ACZ RDE CRC
PDR + ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC)
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: ACZ885 Solution for injection
Other Name: canakinumab |
Experimental: PDR + CJM 25mg Q4W
PDR + CJM 25mg Q4W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: CJM112 Solution for infusion |
Experimental: PDR + CJM 75mg Q4W
PDR + CJM 75mg Q4W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: CJM112 Solution for infusion |
Experimental: PDR + CJM 225mg Q4W
PDR + CJM 225mg Q4W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: CJM112 Solution for infusion |
Experimental: PDR + CJM 450mg Q4W
PDR + CJM 450mg Q4W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: CJM112 Solution for infusion |
Experimental: PDR + CJM 450mg Q2W
PDR + CJM 450mg Q2W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: CJM112 Solution for infusion |
Experimental: PDR + CJM 900mg Q4W
PDR + CJM 900mg Q4W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: CJM112 Solution for infusion |
Experimental: PDR + CJM 900mg Q2W
PDR + CJM 900mg Q2W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: CJM112 Solution for infusion |
Experimental: PDR + CJM 1200mg Q4W
PDR + CJM 1200mg Q4W
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Biological: CJM112 Solution for infusion |
Experimental: PDR + TMT 0.5mg QD
PDR + TMT 0.5mg QD
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Drug: TMT212 Tablets
Other Name: trametinib |
Experimental: PDR + TMT 1mg QD
PDR + TMT 1mg QD
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Drug: TMT212 Tablets
Other Name: trametinib |
Experimental: PDR + TMT 1mg QD, 3 Weeks on/1 Week off
PDR + TMT 1mg QD, 3 Weeks on/1 Week off
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Drug: TMT212 Tablets
Other Name: trametinib |
Experimental: PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off
PDR + TMT 1.5 mg QD, 2 Weeks on/2 Weeks off
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Drug: TMT212 Tablets
Other Name: trametinib |
Experimental: PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off
PDR + TMT 1.5 mg QD, 3 Weeks on/1 Week off
|
Biological: PDR001
Powder for solution for infusion
Other Name: Spartalizumab/PDR001 Drug: TMT212 Tablets
Other Name: trametinib |
Experimental: PDR + EGF816 25mg QD
PDR + EGF816 25mg QD
|
Drug: EGF816
Tablets
Other Name: Nazartinib |
Experimental: PDR + EGF816 50mg QD
PDR + EGF816 50mg QD
|
Drug: EGF816
Tablets
Other Name: Nazartinib |
Experimental: s.a. ACZ RDE TNBC
Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Triple Negative Breast Cancer (TNBC)
|
Biological: ACZ885
Solution for injection
Other Name: canakinumab |
Experimental: s.a. ACZ RDE NSCLC
Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Non-Small Cell Lung Cancer (NSCLC)
|
Biological: ACZ885
Solution for injection
Other Name: canakinumab |
Experimental: s.a. ACZ RDE CRC
Single agent (s.a.) ACZ Recommended Dose for Expansion (RDE) Colorectal Cancer (CRC)
|
Biological: ACZ885
Solution for injection
Other Name: canakinumab |
- 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 ]
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
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.
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
United States, Maryland | |
Sidney Kimmel Comprehensive Cancer Center SC-3 | |
Baltimore, Maryland, United States, 21287-0013 | |
United States, Massachusetts | |
Dana Farber Cancer Center | |
Boston, Massachusetts, United States, 02215 | |
United States, Tennessee | |
Sarah Cannon Research Institute | |
Nashville, Tennessee, United States, 37203 | |
United States, Texas | |
University of Texas MD Anderson Cancer Center | |
Houston, Texas, United States, 77030 | |
Belgium | |
Novartis Investigative Site | |
Brussels, Belgium, BE-B-1200 | |
Novartis Investigative Site | |
Wilrijk, Belgium, 2610 | |
Canada, Ontario | |
Novartis Investigative Site | |
Toronto, Ontario, Canada, M5G 2M9 | |
Canada, Quebec | |
Novartis Investigative Site | |
Montreal, Quebec, Canada, H3T 1E2 | |
France | |
Novartis Investigative Site | |
Lyon Cedex, France, 69373 | |
Novartis Investigative Site | |
Paris, France, 75231 | |
Novartis Investigative Site | |
Toulouse Cedex 9, France, 31059 | |
Novartis Investigative Site | |
Villejuif Cedex, France, 94800 | |
Israel | |
Novartis Investigative Site | |
Tel Aviv, Israel, 6423906 | |
Italy | |
Novartis Investigative Site | |
Milano, MI, Italy, 20132 | |
Novartis Investigative Site | |
Rozzano, MI, Italy, 20089 | |
Singapore | |
Novartis Investigative Site | |
Singapore, Singapore, 119228 | |
Novartis Investigative Site | |
Singapore, Singapore, 169610 | |
Spain | |
Novartis Investigative Site | |
Barcelona, Catalunya, Spain, 08036 | |
Novartis Investigative Site | |
Hospitalet de LLobregat, Catalunya, Spain, 08907 | |
Novartis Investigative Site | |
Madrid, Spain, 28009 | |
Novartis Investigative Site | |
Madrid, Spain, 28050 | |
Taiwan | |
Novartis Investigative Site | |
Tainan, Taiwan, 70403 | |
Novartis Investigative Site | |
Taoyuan, Taiwan, 33305 |
Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT02900664 |
Other Study ID Numbers: |
CPDR001X2103 2016-000633-49 ( EudraCT Number ) |
First Posted: | September 14, 2016 Key Record Dates |
Last Update Posted: | March 29, 2022 |
Last Verified: | March 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
CRC TNBC NSCLC (adenocarcinoma) Immunomodulation Biomarkers Bayesian logistic regression model PDR001 Immunotherapy Rectal cancer Metastatic adenocarcinoma Colorectal cancer colon cancer bowel cancer cancer of the colon and rectum Colorectal adenocarcinoma |
adenocarcinoma colon cancer large intestine large intestine cancer colorectum cancer Triple-negative breast cancer (TNBC) TNBC, basal type secretory cell adenoid cystic medullary ductal carcinoma inflammatory breast carcinoma breast cancer |
Breast Neoplasms Colorectal Neoplasms Adenocarcinoma Triple Negative Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases |
Intestinal Diseases Rectal Diseases Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Trametinib Spartalizumab Nazartinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immune Checkpoint Inhibitors Antineoplastic Agents, Immunological |