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

Study identifier:D6070C00001

ClinicalTrials.gov identifier:NCT02503774

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Solid Tumors

Phase

Phase 1

Healthy volunteers

Study drug

Oleclumab, Durvalumab

Sex

All

Actual Enrollment

192

Study type

Interventional

Age

18 Years - 101 Years

Date

Study Start Date: 24 Jul 2015

Primary Completion Date: 22 Jan 2021

Study Completion Date: 07 Mar 2023

Study design

Allocation: Non-randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2023 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

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

No locations available

Arms	Assigned Interventions
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.
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.
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: 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 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: 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-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.	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-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.	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-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.	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.

Documents available

study-synopsis_Redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Contact Backup

AstraZeneca Cancer Study Locater Service

1-877-400-4656