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A Study of LY3076226 in Participants With Advanced or Metastatic Cancer

Primary Purpose

Advanced Cancer, Metastatic Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LY3076226
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Cancer focused on measuring bladder cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Fox Chase Cancer Center
  • Medical University of South Carolina
  • The START Center for Cancer Care
  • 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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LY3076226

Arm Description

Part A (dose escalation in advanced cancer): LY3076226 administered intravenously (IV) on day 1 of each 21 day cycle. Part B (dose expansion in advanced urothelial carcinoma): LY3076226 administered IV on day 1 of each 21 day cycle.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of LY3076226
The MTD was defined as the highest dose tested that had less than 33% probability of causing a dose limiting toxicity (DLT).

Secondary Outcome Measures

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3076226
PK: Area Under the Concentration-Time Curve (AUC) of LY3076226
Number of Participants With Tumor Response
Tumor response was assessed using confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST version 1.1). Complete response (CR) was the disappearance of all target and non-target lesions and normalization of tumor marker levels of non-target lesions; partial response (PR) was at least a 30% decrease in the sum of the longest diameter of target lesions.

Full Information

First Posted
August 19, 2015
Last Updated
April 9, 2020
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT02529553
Brief Title
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

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
September 2015 (undefined)
Primary Completion Date
March 28, 2018 (Actual)
Study Completion Date
March 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Cancer, Metastatic Cancer
Keywords
bladder cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LY3076226
Arm Type
Experimental
Arm Description
Part A (dose escalation in advanced cancer): LY3076226 administered intravenously (IV) on day 1 of each 21 day cycle. Part B (dose expansion in advanced urothelial carcinoma): LY3076226 administered IV on day 1 of each 21 day cycle.
Intervention Type
Drug
Intervention Name(s)
LY3076226
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of LY3076226
Description
The MTD was defined as the highest dose tested that had less than 33% probability of causing a dose limiting toxicity (DLT).
Time Frame
Cycle 1 (21 Days)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3076226
Time Frame
Predose: Day 1 (Cycle 1) and 63 (Cycle 3); Postdose: 0.05, 1, 3, 6, 24 and 72 hours
Title
PK: Area Under the Concentration-Time Curve (AUC) of LY3076226
Time Frame
Predose: Day 1 (Cycle 1) and 63 (Cycle 3); Postdose: 0.05, 1, 3, 6, 24 and 72 hours
Title
Number of Participants With Tumor Response
Description
Tumor response was assessed using confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST version 1.1). Complete response (CR) was the disappearance of all target and non-target lesions and normalization of tumor marker levels of non-target lesions; partial response (PR) was at least a 30% decrease in the sum of the longest diameter of target lesions.
Time Frame
Baseline through Study Completion (Cycle 3, day 21)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111-2497
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
The START Center for Cancer Care
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
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.
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
34264412
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.
Results Reference
derived
Links:
URL
https://www.lillytrialguide.com/en-US/studies/solid-tumor/JOBA#?postal=
Description
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