MEDI9447 Alone And In Combination With MEDI4736 In Adult Participants With Select Advanced Solid Tumors.

Study Overview

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

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

N/A

Solid Tumors

DRUG: Oleclumab
DRUG: Durvalumab

D6070C00001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-07-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-07-07
First Submitted that Met QC Criteria 2015-07-17	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-07-11
First Posted (ACTUAL) 2015-07-21	Results First Posted N/A	Last Verified 2023-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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.	DRUG: Oleclumab Participants will receive IV infusion of oleclumab as stated in arms' description. DRUG: Durvalumab Participants will receive IV infusion of durvalumab as stated in arms' description.
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.	DRUG: Oleclumab Participants will receive IV infusion of oleclumab as stated in arms' description. DRUG: Durvalumab Participants will receive IV infusion of durvalumab as stated in arms' description.
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.	DRUG: Oleclumab Participants will receive IV infusion of oleclumab as stated in arms' description.
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.	DRUG: Oleclumab Participants will receive IV infusion of oleclumab as stated in arms' description.
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.	DRUG: Oleclumab Participants will receive IV infusion of oleclumab as stated in arms' description. DRUG: Durvalumab Participants will receive IV infusion of durvalumab as stated in arms' description.
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.	DRUG: Oleclumab Participants will receive IV infusion of oleclumab as stated in arms' description. DRUG: Durvalumab Participants will receive IV infusion of durvalumab as stated in arms' description.
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.	DRUG: Durvalumab Participants will receive IV infusion of durvalumab as stated in arms' description.
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.	DRUG: Durvalumab Participants will receive IV infusion of durvalumab as stated in arms' description.
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 developm
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
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 disconti

Primary Outcome Measures	Measure Description	Time Frame
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
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)
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)
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)
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 Outcome Measures	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Rac Ctrough of MEDI4736	The Rac Ctrough of MEDI4736 is reported.	Day 57 (prior to start of MEDI4736 infusion)
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)
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)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: MedImmune LLC, MedImmune LLC

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Bendell J, LoRusso P, Overman M, Noonan AM, Kim DW, Strickler JH, Kim SW, Clarke S, George TJ, Grimison PS, Barve M, Amin M, Desai J, Wise-Draper T, Eck S, Jiang Y, Khan AA, Wu Y, Martin P, Cooper ZA, Elgeioushi N, Mueller N, Kumar R, Patel SP. First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors. Cancer Immunol Immunother. 2023 Jul;72(7):2443-2458. doi: 10.1007/s00262-023-03430-6. Epub 2023 Apr 5.
Hay CM, Sult E, Huang Q, Mulgrew K, Fuhrmann SR, McGlinchey KA, Hammond SA, Rothstein R, Rios-Doria J, Poon E, Holoweckyj N, Durham NM, Leow CC, Diedrich G, Damschroder M, Herbst R, Hollingsworth RE, Sachsenmeier KF. Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology. 2016 Jul 11;5(8):e1208875. doi: 10.1080/2162402X.2016.1208875. eCollection 2016 Aug.

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