Clinical trial NCT02529553: A Study of LY3076226 in Participants With Advanced or Metastatic Cancer
Official title: A Phase 1 Study of LY3076226, a Fibroblast Growth Factor Receptor 3 (FGFR3) Antibody-Drug Conjugate, in Patients With Advanced or Metastatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Metastatic Cancer
Keywords: bladder cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-08-20
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety of the study drug known as LY3076226 in participants with advanced or metastatic cancer.


Eligibility criteria: Inclusion Criteria:

* Have advanced or metastatic cancer and be an appropriate candidate for experimental therapy.

  * Part B: Have a diagnosis of bladder cancer.
  * Part B: Have alterations of FGFR3.
* Have adequate organ function.
* Have discontinued previous treatments for cancer and have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior chemotherapy, surgery, or radiotherapy to Grade ≤1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 (v 4.0).
* If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug. If the participant is a female of childbearing potential, must have had a negative serum or urine pregnancy test within 7 days of the first dose of study drug and must not be breastfeeding.

Exclusion Criteria:

* Have received treatment within 28 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device (other than the study drug/device used in this study) or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
* Have preexisting corneal disease that may interfere with assessment for potential eye toxicity during the study.
* Have preexisting Grade ≥2 skin disorder (for example, erythema, dermatitis).
* Have serious preexisting medical conditions (left to the discretion of the investigator).
* Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 28 days.
* Have current acute or chronic leukemia.
* Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
* Have a second primary malignancy that, in the judgment of the investigator and sponsor, may affect the interpretation of results. Curatively treated nonmelanoma skin cancer or in situ carcinoma of any origin is allowed.
* Have Fridericia-corrected QT interval (QTcF) \>480 milliseconds on screening electrocardiogram (ECG).
* Have a serious cardiac condition, such as congestive heart failure; New York Heart Association Class III/IV heart disease; unstable angina pectoris; myocardial infarction within the last 3 months; valvulopathy that is severe, moderate, or deemed clinically significant; or arrhythmias that are symptomatic or require treatment (not including participants with rate-controlled atrial fibrillation).

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of LY3076226
timeFrame: Cycle 1 (21 Days)
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3076226
timeFrame: Predose: Day 1 (Cycle 1) and 63 (Cycle 3); Postdose: 0.05, 1, 3, 6, 24 and 72 hours
measure: PK: Area Under the Concentration-Time Curve (AUC) of LY3076226
timeFrame: Predose: Day 1 (Cycle 1) and 63 (Cycle 3); Postdose: 0.05, 1, 3, 6, 24 and 72 hours
measure: Number of Participants With Tumor Response
timeFrame: Baseline through Study Completion (Cycle 3, day 21)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: San Antonio
country: United States
facility: The START Center for Cancer Care
state: Texas
city: Vancouver
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.
state: British Columbia
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Kollmannsberger C, Britten CD, Olszanski AJ, Walker JA, Zang W, Willard MD, Radtke DB, Farrington DL, Bell-McGuinn KM, Patnaik A. A phase 1 study of LY3076226, a fibroblast growth factor receptor 3 (FGFR3) antibody-drug conjugate, in patients with advanced or metastatic cancer. Invest New Drugs. 2021 Dec;39(6):1613-1623. doi: 10.1007/s10637-021-01146-x. Epub 2021 Jul 15.