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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03207867
Registration number
NCT03207867
Ethics application status
Date submitted
19/06/2017
Date registered
5/07/2017
Date last updated
1/03/2024
Titles & IDs
Public title
A Phase 2 Study of NIR178 in Combination With PDR001 in Patients With Solid Tumors and Non-Hodgkin Lymphoma
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Scientific title
A Phase 2, Multi-center, Open Label Study of NIR178 in Combination With PDR001 in Patients With Selected Advanced Solid Tumors and Non-Hodgkin Lymphoma
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Secondary ID [1]
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2017-000241-49
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Secondary ID [2]
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CNIR178X2201
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
NSCLC, Non Small Cell Lung Cancer
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RCC, Renal Cell Cancer
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Pancreatic Cancer
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Urothelial Cancer
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Head and Neck Cancer
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0
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DLBCL, Diffused Large B Cell Lymphoma
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MSS, Microsatellite Stable Colon Cancer
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TNBC, Triple Negative Breast Cancer
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Melanoma
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mCRPC, Metastatic Castration Resistant Prostate Cancer
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Condition category
Condition code
Cancer
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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Cancer
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Breast
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Cancer
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Kidney
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - NIR178
Treatment: Drugs - PDR001
Experimental: NIR178 + PDR001 - Part 1: NIR178 continuously in combination with PDR001 400mg every 4 weeks. The part 1 enrolled 9 different tumor types.
Experimental: NIR178 BID Intermittent + PDR001 - Part 2: Three different dosing schedules of NIR178 twice daily (BID) including continuous and two intermittent in combination with PDR001
Experimental: Part 3 - Further evaluation of optimal intermittent or continuous schedule of NIR178 in combination with PDR001 (if selected based on results of Part 2). A film-coated tablet of NIR178 was assessed.
Experimental: Japanese safety run-in part - Different dosing schedules of NIR178 were explored.
Treatment: Drugs: NIR178
NIR178, a new, non-xanthine based compound, is a potent oral adenosine A2a receptor against antagonist being developed by Novartis.
NIR178 was administered orally twice daily (BID) as a capsule (Part 1, Part 2 and Japanese safety run-in) and as a film-coated table (Part 3). There were up to 3 dose levels assessed: 80, 160 and 240 mg. Three alternative dosing schedules were evaluated: continuous (Part 1, Part 2, Part 3, Japanese safety run-in), 2 weeks on/2 weeks off (Part 2) and 1 week on/1 week off (Part 2).
Each cycle consisted of 28 days.
Treatment: Drugs: PDR001
PDR001 is a human monoclonal antibody (MAb) administered on Day 1 of each cycle. PDR001 400 mg was administered via intravenous (i.v.) infusion over 30 minutes every 4 weeks (Q4W).
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Part 1: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
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Assessment method [1]
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ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
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Timepoint [1]
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Up to 3.9 years
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Primary outcome [2]
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Part 1: Overall Response Rate (ORR) Per Cheson 2014 for DLBCL
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Assessment method [2]
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ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL).
For Cheson 2014 criteria, CR= Target nodes/nodal masses must regress to =1.5 cm in longest diameter (LDi), no extralymphatic sites of disease, absent non-measured lesions, organ enlargement regress to normal, no new lesions, and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative); PR= =50% decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes, absent or regressed non-measured lesions, spleen must have regressed by >50% in length beyond normal, and no new lesions.
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Timepoint [2]
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Up to 2.5 years
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Primary outcome [3]
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Part 2: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
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Assessment method [3]
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ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1.
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
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Timepoint [3]
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Up to 4.7 years
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Primary outcome [4]
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0
Part 3: Overall Response Rate (ORR) Per RECIST v1.1 for Solid Tumors
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Assessment method [4]
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ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR), based on local investigator assessment per RECIST v1.1.
For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
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Timepoint [4]
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Up to 0.5 years
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Secondary outcome [1]
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Part 1: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
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Assessment method [1]
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ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
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Timepoint [1]
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Up to 3.9 years
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Secondary outcome [2]
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Part 2: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
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Assessment method [2]
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ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
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Timepoint [2]
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Up to 4.7 years
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Secondary outcome [3]
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Part 3: Overall Response Rate (ORR) Per iRECIST for Solid Tumors
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Assessment method [3]
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ORR is the percentage of patients with a best overall response of complete response (iCR) or partial response (iPR), based on local investigator assessment per immune-related RECIST (iRECIST).
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Timepoint [3]
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Up to 0.5 years
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Secondary outcome [4]
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Part 1: Mean Percentage Change in PSA From Baseline
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Assessment method [4]
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Prostate-specific antigen (PSA) levels were assessed in serum. Rising PSA is generally a manifestation of progression of prostate cancer.
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Timepoint [4]
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Baseline, up to 0.8 years
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Secondary outcome [5]
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Part 1: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
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Assessment method [5]
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DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
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Timepoint [5]
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Up to 3.9 years
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Secondary outcome [6]
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Part 1: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
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Assessment method [6]
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DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
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Timepoint [6]
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Up to 3.9 years
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Secondary outcome [7]
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Part 1: Disease Control Rate (DCR) Per Cheson 2014 for DLBCL
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Assessment method [7]
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DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease (SD), based on local investigator assessment per Cheson 2014 criteria for diffuse large B-cell lymphoma (DLBCL).
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Timepoint [7]
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Up to 2.5 years
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Secondary outcome [8]
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Part 2: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
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Assessment method [8]
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DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
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Timepoint [8]
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Up to 4.7 years
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Secondary outcome [9]
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Part 2: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
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Assessment method [9]
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DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
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Timepoint [9]
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Up to 4.7 years
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Secondary outcome [10]
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Part 3: Disease Control Rate (DCR) Per RECIST v1.1 for Solid Tumors
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Assessment method [10]
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DCR is the percentage of patients with a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR or Non-progressive disease (NCRNPD), based on local investigator assessment per Response Evaluation Criteria for Solid Tumors (RECIST) v1.1.
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Timepoint [10]
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Up to 0.5 years
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Secondary outcome [11]
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Part 3: Disease Control Rate (DCR) Per iRECIST for Solid Tumors
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Assessment method [11]
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DCR is the percentage of patients with a best overall response of complete response (iCR), partial response (iPR), stable disease (iSD) or Non-iCR or Non-unconfirmed progressive disease (NON-iCR or NON-iUPD), based on local investigator assessment per immune-related RECIST (iRECIST).
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Timepoint [11]
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Up to 0.5 years
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Secondary outcome [12]
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Part 1: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
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Assessment method [12]
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DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.
DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [12]
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Up to 3.9 years
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Secondary outcome [13]
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Part 1: Duration Of Response (DOR) Per iRECIST for Solid Tumors
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Assessment method [13]
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DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.
DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [13]
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Up to 3.9 years
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Secondary outcome [14]
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Part 1: Duration Of Response (DOR) Per Cheson 2014 for DLBCL
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Assessment method [14]
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DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per Cheson 2014 criteria for DLBCL. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment. DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [14]
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Up to 2.5 years
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Secondary outcome [15]
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Part 2: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
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Assessment method [15]
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0
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.
DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [15]
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Up to 4.7 years
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Secondary outcome [16]
0
0
Part 2: Duration Of Response (DOR) Per iRECIST for Solid Tumors
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Assessment method [16]
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DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.
DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [16]
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Up to 4.7 years
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Secondary outcome [17]
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0
Part 3: Duration Of Response (DOR) Per RECIST v1.1 for Solid Tumors
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Assessment method [17]
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0
DOR only applies to patients for whom best overall response is complete response (CR) or partial response (PR) based on local investigator assessment per RECIST v1.1. DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.
DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [17]
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Up to 0.5 years
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Secondary outcome [18]
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0
Part 3: Duration Of Response (DOR) Per iRECIST for Solid Tumors
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Assessment method [18]
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0
DOR only applies to patients for whom best overall response is complete response (iCR) or partial response (iPR) based on local investigator assessment per iRECIST. DOR is defined as the time from the date of first documented response (iCR or iPR) to the date of first documented progression or death due to underlying cancer. If a patient did not have an event, DOR was censored at the date of last adequate tumor assessment.
DOR was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [18]
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Up to 0.5 years
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Secondary outcome [19]
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Part 1: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
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Assessment method [19]
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PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1.
PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [19]
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Up to 3.9 years
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Secondary outcome [20]
0
0
Part 1: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
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Assessment method [20]
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PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST.
PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [20]
0
0
Up to 3.9 years
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Secondary outcome [21]
0
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Part 1: Progression-Free Survival (PFS) Per Cheson 2014 for DLBCL
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Assessment method [21]
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PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per Cheson 2014 for DLBCL.
PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [21]
0
0
Up to 2.5 years
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Secondary outcome [22]
0
0
Part 2: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
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Assessment method [22]
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PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1.
PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [22]
0
0
Up to 4.7 years
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Secondary outcome [23]
0
0
Part 2: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
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Assessment method [23]
0
0
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST.
PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [23]
0
0
Up to 4.7 years
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Secondary outcome [24]
0
0
Part 3: Progression-Free Survival (PFS) Per RECIST v1.1 for Solid Tumors
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Assessment method [24]
0
0
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per RECIST v1.1.
PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [24]
0
0
Up to 0.5 years
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Secondary outcome [25]
0
0
Part 3: Progression-Free Survival (PFS) Per iRECIST for Solid Tumors
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Assessment method [25]
0
0
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, whichever happened first. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. Tumor response was based on local investigator assessment per iRECIST.
PFS was analyzed using Kaplan-Meier estimates as defined in the statistical analysis plan.
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Timepoint [25]
0
0
Up to 0.5 years
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Secondary outcome [26]
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Part 1: 2-year Overall Survival (OS)
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Assessment method [26]
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OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan (SAP).
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Timepoint [26]
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2 years
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Secondary outcome [27]
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Part 2: 2-year Overall Survival (OS)
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Assessment method [27]
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OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.
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Timepoint [27]
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0
2 years
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Secondary outcome [28]
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0
Part 3: 2-year Overall Survival (OS)
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Assessment method [28]
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OS represents the percentage of participants who are alive after the start of study treatment. OS at 2 years was estimated using the Kaplan-Meier method as defined in the statistical analysis plan.
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Timepoint [28]
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2 years
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Secondary outcome [29]
0
0
Part 1: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
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Assessment method [29]
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The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
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Timepoint [29]
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Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
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Secondary outcome [30]
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0
Part 2: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
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Assessment method [30]
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The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
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Timepoint [30]
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Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
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Secondary outcome [31]
0
0
Part 3: Change From Baseline in CD8 Percent Marker Area in Tumor Tissue
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Assessment method [31]
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The tumor expression of CD8 was measured by immunohistochemical (IHC) methods. Newly obtained pre- and on-treatment paired tumor samples were required and collected at screening and after approximately two cycles of therapy.
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Timepoint [31]
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Screening and on-treatment (Cycle 2 Day 1 or Day 15). The duration of one cycle was 28 days.
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Secondary outcome [32]
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Part 1, 2 and 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period
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Assessment method [32]
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Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
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Timepoint [32]
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0
Up to 4 years (Part 1), 4.8 years (Part 2) and 0.6 years (Part 3)
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Secondary outcome [33]
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Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of NIR178
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Assessment method [33]
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Number of participants with at least one dose reduction of NIR178 and number of participants with at least one dose interruption of NIR178. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule.
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Timepoint [33]
0
0
Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
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Secondary outcome [34]
0
0
Part 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of PDR001
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Assessment method [34]
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Number of participants with at least one dose reduction of PDR001 and number of participants with at least one dose interruption of PDR001. Dose or schedule adjustments were permitted for patients who did not tolerate the protocol-specified dosing schedule. Dose reductions were not permitted for PDR001.
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Timepoint [34]
0
0
Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
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Secondary outcome [35]
0
0
Part 1, 2 and 3: Dose Intensity of NIR178
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Assessment method [35]
0
0
Dose intensity of NIR178 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days.
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Timepoint [35]
0
0
Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
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Secondary outcome [36]
0
0
Part 1, 2 and 3: Dose Intensity of PDR001
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Assessment method [36]
0
0
Dose intensity of PDR001 was calculated as cumulative actual dose in milligrams divided by duration of exposure in days and then multiplied by 28 days.
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Timepoint [36]
0
0
Up to 3.9 years (Part 1), 4.7 years (Part 2) and 0.5 years (Part 3)
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Secondary outcome [37]
0
0
Part 1, 2 and 3: Number of Participants With Anti-PDR001 Antibodies
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Assessment method [37]
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0
PDR001 immunogenicity was evaluated in serum samples. Patient anti-drug antibodies (ADA) status was defined as follows:
ADA-negative at baseline: ADA-negative sample at baseline
ADA-positive at baseline: ADA-positive sample at baseline
ADA-negative post-baseline: ADA-negative sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples
Treatment-reduced ADA-positive: ADA-positive sample at baseline and at least 1 post-baseline sample, all of which are ADA-negative samples
Treatment-induced ADA-positive: ADA-negative sample at baseline and at least 1 treatment-induced ADA-positive sample
Treatment-boosted ADA-positive: ADA-positive sample at baseline and at least 1 treatment-boosted ADA-positive sample
ADA-inconclusive: patient who does not qualify for any of the above definitions or a patient for which the baseline sample is missing
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Timepoint [37]
0
0
Up to approximately 5 years
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Secondary outcome [38]
0
0
Japan Safety Run-in: Number of Participants With Dose-Limiting Toxicities (DLTs)
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Assessment method [38]
0
0
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade = 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 28 days of treatment with NIR178 as single agent or in combination with PDR001 during the Japan safety run-in part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
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Timepoint [38]
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28 days
Query!
Secondary outcome [39]
0
0
Japan Safety Run-in: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period
Query!
Assessment method [39]
0
0
Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.
The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
Query!
Timepoint [39]
0
0
Up to 0.7 years
Query!
Secondary outcome [40]
0
0
All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NIR178
Query!
Assessment method [40]
0
0
Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Query!
Timepoint [40]
0
0
Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Query!
Secondary outcome [41]
0
0
All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NIR178
Query!
Assessment method [41]
0
0
Pharmacokinetic (PK) parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
Query!
Timepoint [41]
0
0
Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Query!
Secondary outcome [42]
0
0
All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NIR178
Query!
Assessment method [42]
0
0
PK parameters were calculated based on NIR178 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.
Query!
Timepoint [42]
0
0
Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Query!
Secondary outcome [43]
0
0
All Study Parts: Maximum Observed Plasma Concentration (Cmax) of NJI765 (NIR178 Metabolite)
Query!
Assessment method [43]
0
0
NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.
Query!
Timepoint [43]
0
0
Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Query!
Secondary outcome [44]
0
0
All Study Parts: Time to Reach Maximum Plasma Concentration (Tmax) of NJI765 (NIR178 Metabolite)
Query!
Assessment method [44]
0
0
NJI765 is a NIR178 metabolite. Pharmacokinetic (PK) parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.
Query!
Timepoint [44]
0
0
Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Query!
Secondary outcome [45]
0
0
All Study Parts: Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post Dose (AUC0-12hr) of NJI765 (NIR178 Metabolite)
Query!
Assessment method [45]
0
0
NJI765 is a NIR178 metabolite. PK parameters were calculated based on NJI765 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-12hr calculation.
Query!
Timepoint [45]
0
0
Cycle 1 Day 1 (all), Cycle 1 Day 7 (1wk-on/1wk-off), Cycle 1 Day 14 (2wk-on/2wk-off) and Cycle 1 Day 28 (continuous dosing): pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4 and 8 hours after morning dose and 12 hours after evening dose. 1 cycle=28 days
Query!
Secondary outcome [46]
0
0
All Study Parts: Maximum Observed Serum Concentration (Cmax) of PDR001
Query!
Assessment method [46]
0
0
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose.
Query!
Timepoint [46]
0
0
First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
Query!
Secondary outcome [47]
0
0
All Study Parts: Time to Reach Maximum Serum Concentration (Tmax) of PDR001
Query!
Assessment method [47]
0
0
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations.
Query!
Timepoint [47]
0
0
First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
Query!
Secondary outcome [48]
0
0
All Study Parts: Area Under the Serum Concentration-time Curve From Time Zero to 28 Days Post Dose (AUC0-28day) of PDR001
Query!
Assessment method [48]
0
0
PK parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC0-28day calculation.
Query!
Timepoint [48]
0
0
First dose (Cycle 1 Day 1 or Cycle 2 Day 1 for Japanese patients treated with NIR178 80 or 160 mg) and Cycle 3 Day 1: pre-infusion, 1, 168, 336, 504 and 672 hours after end of infusion. Average duration of infusion=30 minutes. 1 cycle=28 days
Query!
Eligibility
Key inclusion criteria
- Male or female patients =18 years of age. For Japan only: written consent is necessary
both from the patient and his/her legal representative if he/she is under the age of
20 years.
- Histologically documented advanced or metastatic solid tumors or lymphomas Part 1:
histologically confirmed renal cell carcinoma (RCC), pancreatic cancer, urothelial
cancer, head and neck cancer, diffuse large B-cell lymphoma (DLBCL), microsatellite
stable (MSS) colon cancer, triple negative breast cancer (TNBC), melanoma, metastatic
castration resistant prostate cancer (mCRPC) Part 2: histologically confirmed
diagnosis of advanced/metastatic NSCLC. For those with mixed histology, there must be
a predominant histology Part 3: histologically confirmed diagnosis of selected
advanced/metastatic malignancies. Part 3 will be opened to further assess TNBC
patients with a PD-L1 SP-142 IC score of 0 (<1%). A second tumor group will be
considered for Part 3 after completion of Part 1.
- Patient (except for those participating in Japanese safety run-in) 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 screening, and again during therapy on this study.
- Safety run-in part in Japanese patients can enroll any tumor type included in part 1,
2 and 3.
The collection of recent sample is permitted under the following conditions (both must be
met):
Biopsy was collected = 6 months before 1st dose of study treatment and available at the
site.
No immunotherapy was given to the patient since collection of biopsy.
- Part 1 - 3 only: Patients (other than those with DLBCL) must previously have received at
least 1 and no more than 3 prior lines of therapy for their disease (with the exception of
IO-pretreated cutaneous melanoma, HNSCC and RCC), unless considered inappropriate for the
patient (e.g. safety concern, label contraindication): Patients with NSCLC must have
received a prior platinum-based combination. Patients with EGFR positive NSCLC with a T790M
mutation must have progressed on osimertinib or discontinued due to toxicity.
Patients with head and neck cancer must have received a prior platinum-containing regimen.
Patients with bladder cancer must have received a prior platinum-containing regimen or be
ineligible for cisplatin.
Patients with renal cell carcinoma must have received a prior VEGF tyrosine kinase
inhibitor (TKI).
Patients with MSS colorectal cancer must have received (or be intolerant to) prior therapy
with fluoropyrimidine-oxaliplatin- and irinotecan- based regimens.
Patients with triple negative breast cancer:. Part 1: must have received a prior
taxane-containing regimen Part 3: should have received no more than 2 prior lines of
therapy including taxane-based chemotherapy and should have a known PD-L1 status as per
local available testing as determined by VENTANA PD-L1 SP142 Assay with IC score of 0 (<1%)
Patients with DLBCL should be limited to those with no available therapies of proven
clinical benefit Patients should have had prior autologous hematopoietic stem cell
transplantation (auto-HSCT) or determined to be ineligible for auto-HSCT.
Patients with melanoma:
BRAF V600E wild type patients: must have received anti-PD-1/PD-L1 single agent, or in
combination with anti-CTLA-4 therapy BRAF V600E mutant patients: must have received prior
anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy. In addition,
subjects must have received prior BRAF V600E inhibitor therapy, either single-agent or in
combination with a MEK inhibitor
Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC):
- Of the 1-3 prior lines of therapy, patients must have received and failed at least one
line of treatment after emergence of castration resistant disease
- Patients must not have received prior immunotherapy (previous immune checkpoint
inhibitors; single agent and/or combination therapy with anti-CTLA-4, anti-PD-1,
anti-PD-L1), except for NSCLC patients enrolled in part 3 and Japanese safety run-in
part.
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional
techniques or as >10 mm with spiral computer tomography (CT) scan, Magnetic Resonance
Imaging (MRI), or calipers by clinical exam.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Ongoing or prior treatment with A2aR inhibitors. Patients previously treated with A2aR
inhibitors for non-oncologic indications (e.g. Parkinson's disease) may be considered
for enrollment on a case by case basis.
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of PDR001, with the exception of intranasal/inhaled corticosteroids or systemic
corticosteroids at physiological doses (not exceeding equivalent of 10 mg/day of
prednisone)
- History of another primary malignancy except for:
Malignancy treated with curative intent and with no known active disease =2 years before
the first dose of study drug and of low potential risk for recurrence Adequately treated
non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated
carcinoma in situ without evidence of disease
- Active or prior documented autoimmune disease within the past 2 years. Patients with
vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the
past 2 years) are not excluded.
- More than 3 prior lines of therapy except for Japanese safety run-in part.
- History of interstitial lung disease or non-infectious pneumonitis
- Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For
cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas,
6 weeks is indicated as washout period. For patients receiving anticancer
immunotherapies, 4 weeks is indicated as the washout period. GnRH therapy to maintain
effective testosterone suppression levels is allowed for mCRPC patients.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Terminated
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
28/08/2017
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
14/02/2023
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
315
Query!
Recruitment in Australia
Recruitment state(s)
NSW
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Blacktown
Query!
Recruitment postcode(s) [1]
0
0
2148 - Blacktown
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Florida
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Maryland
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Texas
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Wisconsin
Query!
Country [6]
0
0
Argentina
Query!
State/province [6]
0
0
Buenos Aires
Query!
Country [7]
0
0
Austria
Query!
State/province [7]
0
0
Salzburg
Query!
Country [8]
0
0
Belgium
Query!
State/province [8]
0
0
Liege
Query!
Country [9]
0
0
Czechia
Query!
State/province [9]
0
0
Czech Republic
Query!
Country [10]
0
0
France
Query!
State/province [10]
0
0
Marseille
Query!
Country [11]
0
0
Germany
Query!
State/province [11]
0
0
Essen
Query!
Country [12]
0
0
Germany
Query!
State/province [12]
0
0
Koeln
Query!
Country [13]
0
0
Italy
Query!
State/province [13]
0
0
MI
Query!
Country [14]
0
0
Italy
Query!
State/province [14]
0
0
Napoli
Query!
Country [15]
0
0
Japan
Query!
State/province [15]
0
0
Tokyo
Query!
Country [16]
0
0
Netherlands
Query!
State/province [16]
0
0
Rotterdam
Query!
Country [17]
0
0
Singapore
Query!
State/province [17]
0
0
Singapore
Query!
Country [18]
0
0
Spain
Query!
State/province [18]
0
0
Catalunya
Query!
Country [19]
0
0
Switzerland
Query!
State/province [19]
0
0
St. Gallen
Query!
Country [20]
0
0
Taiwan
Query!
State/province [20]
0
0
Taipei
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Novartis Pharmaceuticals
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The purpose of this phase 2 study is to evaluate the efficacy and safety of NIR178 in
combination with PDR001 in multiple solid tumors and diffuse large B-cell lymphoma (DLBCL)
and further explore schedule variations of NIR178 to optimize immune activation through
inhibition of A2aR.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT03207867
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03207867
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