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

NCT02503774 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: D6070C00001
• Study Type: interventional
• Target: 192
• Locations: 3 countries
• Sites: 18

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

Conditions

Solid Tumors

Keywords

Solid Tumors,; MEDI9447,; oleclumab,; MEDI4736,; durvalumab,; CD73,; programmed death ligand-1 (PD-L1),; epidermal growth factor receptor mutant (EGFRm) non-small cell lung cancer (NSCLC),; immunotherapy,; pancreatic,; colorectal

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (17)

• Percentage of Participants With Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1

  Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)

• Percentage pf Participants With Disease Control (DC) per RECIST v1.1

  Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)

• Duration of Response (DoR) per RECIST v1.1

  Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)

• Progression-Free Survival (PFS)

  Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)

• Overall Survival (OS)

  Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)

Study Arms (11)

Dose-escalation: Oleclumab Dose 1

EXPERIMENTAL

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

Dose-escalation: Oleclumab Dose 2

EXPERIMENTAL

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

Dose-escalation: Oleclumab Dose 3

EXPERIMENTAL

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

Dose-escalation: Oleclumab Dose 4

EXPERIMENTAL

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

Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1

EXPERIMENTAL

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; Drug: Durvalumab

Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1

EXPERIMENTAL

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; Drug: Durvalumab

Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1

EXPERIMENTAL

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: Oleclumab; Drug: Durvalumab

Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1

EXPERIMENTAL

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: Oleclumab; Drug: Durvalumab

Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1

EXPERIMENTAL

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.

Drug: Oleclumab; Drug: Durvalumab

Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1

EXPERIMENTAL

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.

Drug: Oleclumab; Drug: Durvalumab

Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1

EXPERIMENTAL

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.

Drug: Oleclumab; Drug: Durvalumab

Interventions

Oleclumab DRUG

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

Dose-escalation: Oleclumab Dose 1; Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1; Dose-escalation: Oleclumab Dose 2; Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1; Dose-escalation: Oleclumab Dose 3; Dose-escalation: Oleclumab Dose 4; Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1; Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1; Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1; Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1; Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1

Durvalumab DRUG

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

Dose-escalation: Oleclumab Dose 1 + Durvalumab Dose 1; Dose-escalation: Oleclumab Dose 2 + Durvalumab Dose 1; Dose-escalation: OleclumabDose 3 + Durvalumab Dose 1; Dose-escalation: OleclumabDose 4 + Durvalumab Dose 1; Dose-expansion (CRC): Oleclumab Dose 4 + Durvalumab Dose 1; Dose-expansion (NSCLC): Oleclumab Dose 4 + Durvalumab Dose 1; Dose-expansion (Pancreatic adenocarcinoma): Oleclumab Dose 4+ Durvalumab Dose 1

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (18)

Research Site

La Jolla, California, 92093, United States

Location

Research Site

New Haven, Connecticut, 06510, United States

Location

Research Site

Gainesville, Florida, 32610, United States

Location

Research Site

Atlanta, Georgia, 30318, United States

Location

Research Site

St Louis, Missouri, 63156, United States

Location

Research Site

Durham, North Carolina, 27705, United States

Location

Research Site

Cincinnati, Ohio, 45267, United States

Location

Research Site

Columbus, Ohio, 43210, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Dallas, Texas, 75230, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Camperdown, 2050, Australia

Location

Research Site

Parkville, 3050, Australia

Location

Research Site

St Leonards, 2065, Australia

Location

Research Site

Woolloongabba, 4068, Australia

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Related Publications (2)

• 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.

  PMID: 37016126 DERIVED

• 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.

  PMID: 27622077 DERIVED

Related Links

• study-synopsis\_Redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 21, 2015
• Study Start: July 24, 2015
• Primary Completion: January 22, 2021
• Study Completion: March 7, 2023
• Last Updated: July 11, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (11); AU (4); KR (3)