MEDI9447 Alone and in Combination With MEDI4736 in Adult Participants With Select Advanced Solid Tumors.

Solid Tumors Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02503774
• Other study ID #: D6070C00001
• Status: Completed
• Phase: Phase 1
• Start date: July 24, 2015
• Est. completion date: March 7, 2023

Study information

• Verified date: July 2023
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: March 7, 2023
• Est. primary completion date: January 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 101 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• Oleclumab
Participants will receive IV infusion of oleclumab as stated in arms' description.
• Durvalumab
Participants will receive IV infusion of durvalumab as stated in arms' description.

Locations

Country	Name	City	State
Australia	Research Site	Camperdown
Australia	Research Site	Parkville
Australia	Research Site	St Leonards
Australia	Research Site	Woolloongabba
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
United States	Research Site	Atlanta	Georgia
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Durham	North Carolina
United States	Research Site	Gainesville	Florida
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Haven	Connecticut
United States	Research Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Australia,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities (DLTs) in Dose-escalation Phase	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).	From Day 1 to Day 28 after first dose of study drug
Primary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	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.	From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
Primary	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs	Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, thyroid function tests, coagulation, and urinalysis.	From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
Primary	Number of Participants With Abnormal Vital Signs Reported as TEAEs	Participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.	From Day 1 through 188.1 weeks (corresponding to maximum observed duration)
Primary	Number of Participants With Change From Baseline in QTcF	Number of participants with change from Baseline in QTcF (> 60 msec and > 90 msec) is reported.	Baseline (prior to Day 1 dose) through 188.1 weeks (corresponding to maximum observed duration)
Secondary	Percentage of Participants With Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1	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.	Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary	Percentage pf Participants With Disease Control (DC) per RECIST v1.1	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.	Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary	Duration of Response (DoR) per RECIST v1.1	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.	Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary	Progression-Free Survival (PFS)	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.	Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary	Overall Survival (OS)	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.	Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary	Maximum Observed Serum Concentration (Cmax) of MEDI9447	The Cmax of MEDI9447 (oleclumab) for Cycle 1 and at steady state (Day 57) are reported.	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)
Secondary	Area Under the Serum Concentration Time Curve From 0 To 14 Days Post First Dose [AUC(0-14)] of MEDI9447	The AUC(0-14) of MEDI9447 is reported.	Day 1 (pre-dose; 10 minutes and 2 hours post end of infusion)
Secondary	Time To Maximum Observed Serum Concentration (Tmax) of MEDI9447	The Tmax of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 are reported.	Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
Secondary	Observed Lowest Serum Concentration Reached Before the Next Dose (Ctrough) of MEDI9447	The Ctrough of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 are reported.	Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
Secondary	Accumulation Ratio for Cmax (Rac Cmax) of MEDI9447	The Rac Cmax of MEDI9447 for Cycle 1 and at steady state (Day 57) of MEDI9447 is reported.	Day 57 (pre-dose; 10 minutes post end of infusion)
Secondary	Accumulation Ratio for Ctrough (Rac Ctrough) of MEDI9447	The Rac Ctrough of MEDI9447 is reported.	Day 57 (pre-dose; 10 minutes post end of infusion)
Secondary	Cmax of MEDI4736	The Cmax of MEDI4736 (durvalumab) is reported.	Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
Secondary	Tmax of MEDI4736	The Tmax of MEDI4736 is reported.	Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
Secondary	Ctrough of MEDI4736	The Ctrough of MEDI4736 for Cycle 1 and at steady state (Day 57) are reported.	Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion), Day 57 (prior to start of MEDI9447 infusion)
Secondary	Rac Ctrough of MEDI4736	The Rac Ctrough of MEDI4736 is reported.	Day 57 (prior to start of MEDI4736 infusion)
Secondary	Number of Participants With Positive Anti-Drug Antibody Response (ADA) to MEDI9447	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).	Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
Secondary	Number of Participants With Positive ADA to MEDI4736	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).	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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