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

MedImmune LLC192 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

192

Conditions

Solid Tumors

Interventions

OleclumabDRUG

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

DurvalumabDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 101 Years

Medical Language ↔ Plain English

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

Locations (18)

Research Site

La Jolla, California, United States

Research Site

New Haven, Connecticut, United States

Research Site

Outcomes

Primary Outcomes

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).

Time frame: 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.

Time frame: 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.

Time frame: From Day 1 through 200.1 weeks (corresponding to maximum observed duration)

Data from ClinicalTrials.gov

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Secondary Outcomes

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

The OR is defined as confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, and no new lesions. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline, and the non-target lesion at least stable with no evidence of new lesions. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. Percentage of participants with OR are reported.