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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/NCT02503774
Registration number
NCT02503774
Ethics application status
Date submitted
6/07/2015
Date registered
21/07/2015
Date last updated
11/07/2023
Titles & IDs
Public title
MEDI9447 Alone and in Combination With MEDI4736 in Adult Participants With Select Advanced Solid Tumors.
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Scientific title
A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors
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Secondary ID [1]
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D6070C00001
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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:
Solid Tumors
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Oleclumab
Treatment: Drugs - Durvalumab
Experimental: Dose-escalation: Oleclumab Dose 1 - Participants will receive oleclumab Dose 1 intravenously (IV) every two weeks (Q2W) until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-escalation: Oleclumab Dose 2 - Participants will receive oleclumab Dose 2 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-escalation: Oleclumab Dose 3 - Participants will receive oleclumab Dose 3 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-escalation: Oleclumab Dose 4 - Participants will receive oleclumab Dose 4 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1 - Participants will receive oleclumab Dose 1 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1 - Participants will receive oleclumab Dose 2 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1 - Participants will receive oleclumab Dose 3 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1 - Participants will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1 - Participants with previously treated microsatellite stable-colorectal cancer (MSS-CRC) will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1 - Participants with previously treated pancreatic adenocarcinoma will receive oleclumab Dose 4 IV Q2W followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Experimental: Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1 - Participants with previously treated EGFRm NSCLC will receive oleclumab Dose 4 IV followed by durvalumab Dose 1 IV Q2W until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurs first.
Treatment: Drugs: Oleclumab
Participants will receive IV infusion of oleclumab as stated in arms' description.
Treatment: Drugs: Durvalumab
Participants will receive IV infusion of durvalumab as stated in arms' description.
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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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Number of Participants With Dose Limiting Toxicities (DLTs) in Dose-escalation Phase
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Assessment method [1]
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A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period, which included any Grade 4 immune-mediated adverse event (imAE), any >= Grade 3 colitis, any Grade 3 or 4 non-infectious pneumonitis irrespective of duration, any Grade 3 imAE (excluding colitis or pneumonitis, did not downgrade to <= Grade 2 within 3 days after onset of the event despite maximal medical supportive care including systemic corticosteroids or did not downgrade to <= Grade 1 or baseline within 14 days), liver transaminase elevation >= 5 × but <= 8 × upper limit of normal (ULN) that did not downgrade to Grade 2 within 5 days after onset with optimal medical management (including systemic corticosteroids), transaminase elevation > 8 × ULN or total bilirubin (TBL) > 5 × ULN regardless of duration or reversibility, or any increase in aspartate aminotransferase or alanine aminotransferase > 3 × ULN and concurrent increase in TBL > 2 × ULN (Hy's Law).
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Timepoint [1]
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From Day 1 to Day 28 after first dose of study drug
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Primary outcome [2]
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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Assessment method [2]
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An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
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Timepoint [2]
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From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
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Primary outcome [3]
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Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
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Assessment method [3]
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Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, coagulation, and urinalysis.
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Timepoint [3]
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From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
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Primary outcome [4]
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Number of Participants With Abnormal Vital Signs Reported as TEAEs
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Assessment method [4]
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Participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.
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Timepoint [4]
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From Day 1 through 188.1 weeks (corresponding to maximum observed duration)
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Primary outcome [5]
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Number of Participants With Change From Baseline in QTcF
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Assessment method [5]
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Number of participants with change from Baseline in QTcF (> 60 msec and > 90 msec) is reported.
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Timepoint [5]
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Baseline (prior to Day 1 dose) through 188.1 weeks (corresponding to maximum observed duration)
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Secondary outcome [1]
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Percentage of Participants With Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
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Assessment method [1]
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The OR is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, and no new lesions. The PR is defined as >= 30% decrease in the sum of the diameters of target lesions compared to baseline, and the non-target lesion at least stable with no evidence of new lesions. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. Percentage of participants with OR are reported.
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Timepoint [1]
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Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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Secondary outcome [2]
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Percentage pf Participants With Disease Control (DC) per RECIST v1.1
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Assessment method [2]
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The DC is defined as CR, PR, or stable disease (SD) which was maintained by >= 8 weeks from the start of treatment. The SD is defined as neither sufficient shrinkage of target lesion to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study and non-progressive disease and not evaluable or no non-target lesion. The CR is defined as disappearance of all target and non-target lesions, and no new lesions. The PR is defined as >= 30% decrease in the sum of the diameters of target lesions compared to baseline, and the non-target lesion at least stable with no evidence of new lesions. Percentage of participants with DC at >= 8 weeks, >= 16 weeks, and >= 24 weeks are reported.
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Timepoint [2]
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Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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Secondary outcome [3]
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Duration of Response (DoR) per RECIST v1.1
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Assessment method [3]
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The DoR is defined as the duration from the first documentation of OR (confirmed CR or PR) to the first documented PD or death due to any cause, whichever occurred first. The CR is defined as disappearance of all target and non-target lesions, and no new lesions. The PR is defined as >= 30% decrease in the sum of the diameters of target lesions compared to baseline, and the non-target lesion at least stable with no evidence of new lesions. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. The PD is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The DoR was estimated using Kaplan-Meier method.
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Timepoint [3]
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Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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Secondary outcome [4]
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Progression-Free Survival (PFS)
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Assessment method [4]
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The PFS is defined as the time from the start of study treatment until the documentation of PD based on RECIST version 1.1 or death due to any cause, whichever occurred first. The PD is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. The PFS was estimated using Kaplan-Meier method.
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Timepoint [4]
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Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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Secondary outcome [5]
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Overall Survival (OS)
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Assessment method [5]
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The OS is defined as the time from the start of treatment with study drug until death due to any cause. The OS was estimated using Kaplan-Meier method.
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Timepoint [5]
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Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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Secondary outcome [6]
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Maximum Observed Serum Concentration (Cmax) of MEDI9447
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Assessment method [6]
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The Cmax of MEDI9447 (oleclumab) for Cycle 1 and at steady state (Day 57) are reported.
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Timepoint [6]
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Day 1 (pre-dose, and 10 minutes and 2 hours post end of infusion), Day 57 (pre-dose and 10 minutes post end of infusion)
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Secondary outcome [7]
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Area Under the Serum Concentration Time Curve From 0 To 14 Days Post First Dose [AUC(0-14)] of MEDI9447
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Assessment method [7]
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The AUC(0-14) of MEDI9447 is reported.
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Timepoint [7]
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Day 1 (pre-dose; 10 minutes and 2 hours post end of infusion)
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Secondary outcome [8]
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Time To Maximum Observed Serum Concentration (Tmax) of MEDI9447
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Assessment method [8]
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The Tmax of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 are reported.
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Timepoint [8]
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Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
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Secondary outcome [9]
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Observed Lowest Serum Concentration Reached Before the Next Dose (Ctrough) of MEDI9447
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Assessment method [9]
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The Ctrough of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 are reported.
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Timepoint [9]
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Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
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Secondary outcome [10]
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Accumulation Ratio for Cmax (Rac Cmax) of MEDI9447
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Assessment method [10]
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The Rac Cmax of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 is reported.
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Timepoint [10]
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Day 57 (pre-dose; 10 minutes post end of infusion)
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Secondary outcome [11]
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Accumulation Ratio for Ctrough (Rac Ctrough) of MEDI9447
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Assessment method [11]
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The Rac Ctrough of MEDI9447 is reported.
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Timepoint [11]
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Day 57 (pre-dose; 10 minutes post end of infusion)
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Secondary outcome [12]
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Cmax of MEDI4736
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Assessment method [12]
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The Cmax of MEDI4736 (durvalumab) is reported.
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Timepoint [12]
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Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
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Secondary outcome [13]
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Tmax of MEDI4736
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Assessment method [13]
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The Tmax of MEDI4736 is reported.
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Timepoint [13]
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Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
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Secondary outcome [14]
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Ctrough of MEDI4736
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Assessment method [14]
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The Ctrough of MEDI4736 for Cycle 1 and at steady state (Day 57) are reported.
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Timepoint [14]
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Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion), Day 57 (prior to start of MEDI9447 infusion)
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Secondary outcome [15]
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Rac Ctrough of MEDI4736
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Assessment method [15]
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The Rac Ctrough of MEDI4736 is reported.
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Timepoint [15]
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Day 57 (prior to start of MEDI4736 infusion)
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Secondary outcome [16]
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Number of Participants With Positive Anti-Drug Antibody Response (ADA) to MEDI9447
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Assessment method [16]
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Number of participants with positive ADA to MEDI9447 is reported. Persistent positive was defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive was defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with < 16 weeks between first and last positive).
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Timepoint [16]
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Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
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Secondary outcome [17]
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Number of Participants With Positive ADA to MEDI4736
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Assessment method [17]
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Number of participants with positive ADA to MEDI4736 is reported. Persistent positive was defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive was defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with < 16 weeks between first and last positive).
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Timepoint [17]
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Day 1 through 200.1 weeks (Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
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Eligibility
Key inclusion criteria
- Adult participants; age = 18
- Written and signed informed consent must be obtained
- Have histologic or cytologic documentation of solid tumor including EGFRm NSCLC
- Participants must have at least 1 lesion that is measurable using RECIST guidelines
- Participants must consent to provide archived tumor specimens or tumor biopsies for
correlative biomarker studies.
- Eastern Cooperative Oncology Group performance score of 0 or 1
- Adequate organ function
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Minimum age
18
Years
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Maximum age
101
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Prior treatment with tumor necrosis factor receptor superfamily agonists including
OX40, CD27, CD137 (4-1BB), CD357 (GITR). One cohort also excludes anti CTLA-4, PD-L1,
and anti PD-L1.
- Participants who have received prior therapy with regimens containing CTLA-4, PD-L1,
or PD-1 antagonists may be permitted to enroll under certain conditions
- Cardiac or peripheral vascular disease meeting any of the following criteria:
- Past history of myocardial infarction in the prior 12 months
- Past history of stroke or transient ischemic attack requiring medical therapy
- Congestive heart failure = Class 3 based on New York Heart Association Functional
Classification
- Grade 3 or greater edema (eg, peripheral, pulmonary)
- History of Grade 3 or greater thromboembolic events in the prior 12 months
- Participants with active tuberculosis are ineligible. In settings where there is
clinical or radiographic evidence of tuberculosis, active disease must be ruled out
- Active or prior documented autoimmune or inflammatory disorders
- Untreated central nervous system (CNS) metastatic disease
- Known positive for human immunodeficiency virus (HIV), chronic or active hepatitis B
or active hepatitis A or C
- Other invasive malignancy within 2 years except for noninvasive malignancies such as
cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the
skin, ductal carcinoma in situ of the breast that has been surgically cured
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, active peptic ulcer disease or gastritis, uncontrolled hypertension,
uncontrolled diabetes, or psychiatric illness/social situations that would limit
compliance with study requirement
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
24/07/2015
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
7/03/2023
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Sample size
Target
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Accrual to date
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Final
192
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Research Site - Camperdown
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Recruitment hospital [2]
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Research Site - Parkville
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Recruitment hospital [3]
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Research Site - St Leonards
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Recruitment hospital [4]
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Research Site - Woolloongabba
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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3050 - Parkville
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Recruitment postcode(s) [3]
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2065 - St Leonards
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Recruitment postcode(s) [4]
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4068 - Woolloongabba
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Connecticut
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Country [3]
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United States of America
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State/province [3]
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Florida
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Country [4]
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United States of America
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State/province [4]
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Georgia
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Country [5]
0
0
United States of America
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State/province [5]
0
0
Missouri
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Country [6]
0
0
United States of America
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State/province [6]
0
0
North Carolina
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Country [7]
0
0
United States of America
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State/province [7]
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0
Ohio
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Country [8]
0
0
United States of America
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State/province [8]
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Tennessee
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Country [9]
0
0
United States of America
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State/province [9]
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Texas
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Country [10]
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0
Korea, Republic of
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State/province [10]
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Seoul
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
MedImmune LLC
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics,
Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination with MEDI4736 in
Adult Participants with Select Advanced Solid Tumors
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02503774
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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MedImmune LLC
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Address
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MedImmune LLC
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Country
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Phone
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Fax
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Email
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0
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02503774
Download to PDF