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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02503774




Registration number
NCT02503774
Ethics application status
Date submitted
6/07/2015
Date registered
21/07/2015
Date last updated
11/07/2023

Titles & IDs
Public title
MEDI9447 Alone and in Combination With MEDI4736 in Adult Participants With Select Advanced Solid Tumors.
Scientific 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
Secondary ID [1] 0 0
D6070C00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Oleclumab
Treatment: Drugs - Durvalumab

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.


Treatment: Drugs: Oleclumab
Participants will receive IV infusion of oleclumab as stated in arms' description.

Treatment: Drugs: Durvalumab
Participants will receive IV infusion of durvalumab as stated in arms' description.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose Limiting Toxicities (DLTs) in Dose-escalation Phase
Timepoint [1] 0 0
From Day 1 to Day 28 after first dose of study drug
Primary outcome [2] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Timepoint [2] 0 0
From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
Primary outcome [3] 0 0
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Timepoint [3] 0 0
From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
Primary outcome [4] 0 0
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Timepoint [4] 0 0
From Day 1 through 188.1 weeks (corresponding to maximum observed duration)
Primary outcome [5] 0 0
Number of Participants With Change From Baseline in QTcF
Timepoint [5] 0 0
Baseline (prior to Day 1 dose) through 188.1 weeks (corresponding to maximum observed duration)
Secondary outcome [1] 0 0
Percentage of Participants With Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Timepoint [1] 0 0
Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary outcome [2] 0 0
Percentage pf Participants With Disease Control (DC) per RECIST v1.1
Timepoint [2] 0 0
Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary outcome [3] 0 0
Duration of Response (DoR) per RECIST v1.1
Timepoint [3] 0 0
Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary outcome [4] 0 0
Progression-Free Survival (PFS)
Timepoint [4] 0 0
Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
Secondary outcome [6] 0 0
Maximum Observed Serum Concentration (Cmax) of MEDI9447
Timepoint [6] 0 0
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 outcome [7] 0 0
Area Under the Serum Concentration Time Curve From 0 To 14 Days Post First Dose [AUC(0-14)] of MEDI9447
Timepoint [7] 0 0
Day 1 (pre-dose; 10 minutes and 2 hours post end of infusion)
Secondary outcome [8] 0 0
Time To Maximum Observed Serum Concentration (Tmax) of MEDI9447
Timepoint [8] 0 0
Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
Secondary outcome [9] 0 0
Observed Lowest Serum Concentration Reached Before the Next Dose (Ctrough) of MEDI9447
Timepoint [9] 0 0
Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
Secondary outcome [10] 0 0
Accumulation Ratio for Cmax (Rac Cmax) of MEDI9447
Timepoint [10] 0 0
Day 57 (pre-dose; 10 minutes post end of infusion)
Secondary outcome [11] 0 0
Accumulation Ratio for Ctrough (Rac Ctrough) of MEDI9447
Timepoint [11] 0 0
Day 57 (pre-dose; 10 minutes post end of infusion)
Secondary outcome [12] 0 0
Cmax of MEDI4736
Timepoint [12] 0 0
Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
Secondary outcome [13] 0 0
Tmax of MEDI4736
Timepoint [13] 0 0
Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
Secondary outcome [14] 0 0
Ctrough of MEDI4736
Timepoint [14] 0 0
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 outcome [15] 0 0
Rac Ctrough of MEDI4736
Timepoint [15] 0 0
Day 57 (prior to start of MEDI4736 infusion)
Secondary outcome [16] 0 0
Number of Participants With Positive Anti-Drug Antibody Response (ADA) to MEDI9447
Timepoint [16] 0 0
Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
Secondary outcome [17] 0 0
Number of Participants With Positive ADA to MEDI4736
Timepoint [17] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
101 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/07/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/03/2023
Sample size
Target
Accrual to date
Final
192
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Parkville
Recruitment hospital [3] 0 0
Research Site - St Leonards
Recruitment hospital [4] 0 0
Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
4068 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT02503774
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
MedImmune LLC
Address 0 0
MedImmune LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02503774