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

NCT ID: NCT02503774

Last Updated: 2023-07-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

192 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-24

Study Completion Date

2023-03-07

Brief Summary

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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

Detailed Description

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Conditions

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Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

Durvalumab

Intervention Type DRUG

Participants will receive IV infusion of durvalumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

Durvalumab

Intervention Type DRUG

Participants will receive IV infusion of durvalumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

Durvalumab

Intervention Type DRUG

Participants will receive IV infusion of durvalumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

Durvalumab

Intervention Type DRUG

Participants will receive IV infusion of durvalumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

Durvalumab

Intervention Type DRUG

Participants will receive IV infusion of durvalumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

Durvalumab

Intervention Type DRUG

Participants will receive IV infusion of durvalumab as stated in arms' description.

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.

Group Type EXPERIMENTAL

Oleclumab

Intervention Type DRUG

Participants will receive IV infusion of oleclumab as stated in arms' description.

Durvalumab

Intervention Type DRUG

Participants will receive IV infusion of durvalumab as stated in arms' description.

Interventions

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Oleclumab

Participants will receive IV infusion of oleclumab as stated in arms' description.

Intervention Type DRUG

Durvalumab

Participants will receive IV infusion of durvalumab as stated in arms' description.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

101 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MedImmune LLC

Role: STUDY_DIRECTOR

MedImmune LLC

Locations

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Research Site

La Jolla, California, United States

Site Status

Research Site

New Haven, Connecticut, United States

Site Status

Research Site

Gainesville, Florida, United States

Site Status

Research Site

Atlanta, Georgia, United States

Site Status

Research Site

St Louis, Missouri, United States

Site Status

Research Site

Durham, North Carolina, United States

Site Status

Research Site

Cincinnati, Ohio, United States

Site Status

Research Site

Columbus, Ohio, United States

Site Status

Research Site

Nashville, Tennessee, United States

Site Status

Research Site

Dallas, Texas, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Camperdown, , Australia

Site Status

Research Site

Parkville, , Australia

Site Status

Research Site

St Leonards, , Australia

Site Status

Research Site

Woolloongabba, , Australia

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Countries

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United States Australia South Korea

References

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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.

Reference Type DERIVED
PMID: 37016126 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27622077 (View on PubMed)

Other Identifiers

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D6070C00001

Identifier Type: -

Identifier Source: org_study_id

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