Clinical trial NCT02503774: MEDI9447 Alone and in Combination With MEDI4736 in Adult Participants With Select Advanced Solid Tumors.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2015-07-21
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in Dose-escalation Phase
timeFrame: From Day 1 to Day 28 after first dose of study drug
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: From Day 1 through 200.1 weeks (corresponding to maximum observed duration)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: From Day 1 through 188.1 weeks (corresponding to maximum observed duration)
measure: Number of Participants With Change From Baseline in QTcF
timeFrame: Baseline (prior to Day 1 dose) through 188.1 weeks (corresponding to maximum observed duration)
Secondary outcomes:
measure: Percentage of Participants With Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
timeFrame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
measure: Percentage pf Participants With Disease Control (DC) per RECIST v1.1
timeFrame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
measure: Duration of Response (DoR) per RECIST v1.1
timeFrame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
measure: Overall Survival (OS)
timeFrame: Baseline (Days -28 to -1) through 53 months (corresponding to maximum observed duration)
measure: Maximum Observed Serum Concentration (Cmax) of MEDI9447
timeFrame: 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)
measure: Area Under the Serum Concentration Time Curve From 0 To 14 Days Post First Dose [AUC(0-14)] of MEDI9447
timeFrame: Day 1 (pre-dose; 10 minutes and 2 hours post end of infusion)
measure: Time To Maximum Observed Serum Concentration (Tmax) of MEDI9447
timeFrame: Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
measure: Observed Lowest Serum Concentration Reached Before the Next Dose (Ctrough) of MEDI9447
timeFrame: Day 1 (pre-dose; 10 minutes, 2 hours post end of infusion); Day 57 (pre-dose; 10 minutes post end of infusion)
measure: Accumulation Ratio for Cmax (Rac Cmax) of MEDI9447
timeFrame: Day 57 (pre-dose; 10 minutes post end of infusion)
measure: Accumulation Ratio for Ctrough (Rac Ctrough) of MEDI9447
timeFrame: Day 57 (pre-dose; 10 minutes post end of infusion)
measure: Cmax of MEDI4736
timeFrame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
measure: Tmax of MEDI4736
timeFrame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion)
measure: Ctrough of MEDI4736
timeFrame: Day 1 (prior to start of MEDI9447 infusion and 10 minutes post end of MEDI4736 infusion), Day 57 (prior to start of MEDI9447 infusion)
measure: Rac Ctrough of MEDI4736
timeFrame: Day 57 (prior to start of MEDI4736 infusion)
measure: Number of Participants With Positive Anti-Drug Antibody Response (ADA) to MEDI9447
timeFrame: Day 1 through 192.3 weeks (Days 1 , 29, and 57, EOT, and 30 days post end of treatment)
measure: Number of Participants With Positive ADA to MEDI4736
timeFrame: 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)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Camperdown
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: St Leonards
country: Australia
facility: Research Site
city: Woolloongabba
country: Australia
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: 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.