Oleclumab
DrugParticipants will receive IV infusion of oleclumab as stated in arms' description.
NCT Number: NCT02503774
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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Notify Me18 year–101 year
All sexes
Interventional
Phase 1
Research Site, Camperdown, Australia
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Participants will receive IV infusion of oleclumab as stated in arms' description.
Participants will receive IV infusion of durvalumab as stated in arms' description.
Time frame: From Day 1 to Day 28 after first dose of study drug
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).
Time frame: From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
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.
Time frame: From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, coagulation, and urinalysis.
Time frame: From Day 1 through 188.1 weeks (corresponding to maximum observed duration)
Participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.
Time frame: Baseline (prior to Day 1 dose) through 188.1 weeks (corresponding to maximum observed duration)
Number of participants with change from Baseline in QTcF (> 60 msec and > 90 msec) is reported.
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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.
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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.
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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.
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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.
Time frame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
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.
Time frame: 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)
The Cmax of MEDI9447 (oleclumab) for Cycle 1 and at steady state (Day 57) are reported.
Time frame: Day 1 (pre-dose; 10 minutes and 2 hours post end of infusion)
The AUC(0-14) of MEDI9447 is reported.
Time frame: Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
The Tmax of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 are reported.
Time frame: Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
The Ctrough of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 are reported.
Time frame: Day 57 (pre-dose; 10 minutes post end of infusion)
The Rac Cmax of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 is reported.
Time frame: Day 57 (pre-dose; 10 minutes post end of infusion)
The Rac Ctrough of MEDI9447 is reported.
Time frame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
The Cmax of MEDI4736 (durvalumab) is reported.
Time frame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
The Tmax of MEDI4736 is reported.
Time frame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion), Day 57 (prior to start of MEDI9447 infusion)
The Ctrough of MEDI4736 for Cycle 1 and at steady state (Day 57) are reported.
Time frame: Day 57 (prior to start of MEDI4736 infusion)
The Rac Ctrough of MEDI4736 is reported.
Time frame: Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
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).
Time frame: 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)
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).
MedImmune LLC
Industry
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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View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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