Clinical Trials List
Protocol NumberCPDR001X2103
NCT Number(ClinicalTrials.gov Identfier)NCT02900664
Completed
2017-01-15 - 2020-01-31
Phase I
Terminated1
Study ended1
Phase Ib, open-label, multi-center study to characterize the safety, tolerability and pharmacodynamics (PD) of PDR001 in combination with CJM112, EGF816, IlarisR (canakinumab) or MekinistR (trametinib)
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
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Update
2026/08/24
Investigators and Locations
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Principal Investigator
Ming-Mo Hou
Linkou Chang Gung Medical Foundation
Taiwan National PI
侯明模
Co-Principal Investigator
- Yung-Chang Lin Division of Hematology & Oncology
- Wen-Cheng Chang Division of Hematology & Oncology
- Chih-Liang Wang Division of Hematology & Oncology
- Tsai-Sheng Yang Division of Hematology & Oncology
- Wen-Chi Shen Division of Hematology & Oncology
- Hung-Chih Hsu Division of Hematology & Oncology
- Tse-Ching Chen Division of Others -
- 呂嘉偉 Division of Radiology
The Actual Total Number of Participants Enrolled
1 Study ended
Audit
CRO
Condition/Disease
Colorectal Cancer, Triple Negative Breast Cancer, NSCLC - Adenocarcinoma
Objectives
Primary objective: To characterize the safety and tolerability of PDR001 in combination
with canakinumab, CJM112, trametinib or EGF816, and to identify recommended doses and
schedules for future studies.
Key Secondary objective: To characterize changes in the immune infiltrate in tumors.
Test Drug
PDR001、CJM112、ACZ885/Ilaris® 、EGF816、TMT212/Mekinist®
Active Ingredient
Dosage Form
Dosage
100 mg powder for solution for infusion
150mg/1 mL Solution for infusion/injection
25 mg/50 mg film-coated tablet
150 mg powder for solution for injection
0.5 mg/2 mg film-coated tablet
150mg/1 mL Solution for infusion/injection
25 mg/50 mg film-coated tablet
150 mg powder for solution for injection
0.5 mg/2 mg film-coated tablet
Endpoints
Tumor response assessment as per RECIST version 1.1 and irRC:
Best Overall Response (BOR)
Progression Free Survival (PFS)
Treatment Free Survival (TFS)
Biomarkers: Immune infiltration in tumors:
Histopathology of Tumor Infiltrating Lymphocytes (TILs) by H&E stain,
characterization of TILs and myeloid cell infiltrate by IHC (such as CD8, FoxP3
and myeloid markers as appropiate).
Physical examination
Vital signs
Laboratory evaluations
ECGs
Presence and/or concentration of anti-PDR001 antibodies
Frequency, duration and severity of adverse events
Eye and cardiac assessments (for PDR001+trametinib only)
Best Overall Response (BOR)
Progression Free Survival (PFS)
Treatment Free Survival (TFS)
Biomarkers: Immune infiltration in tumors:
Histopathology of Tumor Infiltrating Lymphocytes (TILs) by H&E stain,
characterization of TILs and myeloid cell infiltrate by IHC (such as CD8, FoxP3
and myeloid markers as appropiate).
Physical examination
Vital signs
Laboratory evaluations
ECGs
Presence and/or concentration of anti-PDR001 antibodies
Frequency, duration and severity of adverse events
Eye and cardiac assessments (for PDR001+trametinib only)
Inclution Criteria
Age ≥ 18 years.
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:
CRC (not mismatch repair deficient by local assay including PCR and/or IHC)
NSCLC (adenocarcinoma)
TNBC(Disease must be negative immunohistochemically for estrogen and
progesterone receptors (≤1% of nuclei positive by IHC) and must not have Her2
overexpression (by Herceptest or validated IHC assay; 0-1+ staining). In cases of
ambiguous Her2 expression (2+ staining), Her2 amplification must be negative (by
FISH or equivalent assay))
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.
Documented approval from Novartis is required prior to study entry.
Written informed consent must be obtained prior to any screening procedures other
than procedures performed as part of standard of care.
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:
CRC (not mismatch repair deficient by local assay including PCR and/or IHC)
NSCLC (adenocarcinoma)
TNBC(Disease must be negative immunohistochemically for estrogen and
progesterone receptors (≤1% of nuclei positive by IHC) and must not have Her2
overexpression (by Herceptest or validated IHC assay; 0-1+ staining). In cases of
ambiguous Her2 expression (2+ staining), Her2 amplification must be negative (by
FISH or equivalent assay))
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.
Documented approval from Novartis is required prior to study entry.
Written informed consent must be obtained prior to any screening procedures other
than procedures performed as part of standard of care.
Exclusion Criteria
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.
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.
The Estimated Number of Participants
-
Taiwan
4 participants
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Global
283 participants
