Trial Title:
A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
NCT ID:
NCT05614739
Condition:
Urinary Bladder Neoplasms
Neoplasm Metastasis
Ureteral Neoplasms
Conditions: Official terms:
Neoplasms
Neoplasm Metastasis
Urinary Bladder Neoplasms
Ureteral Neoplasms
Pembrolizumab
Conditions: Keywords:
Bladder Cancer
Bladder Urothelial Carcinoma
Urinary Bladder Cancer
Urinary Tract Cancer
Renal Pelvis Cancer
Ureter Cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LOXO-435
Description:
Oral
Arm group label:
Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation
Arm group label:
Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization
Arm group label:
Phase 1b: Cohort B1 LOXO-435 Monotherapy Dose Expansion
Arm group label:
Phase 1b: Cohort B2 LOXO-435 Monotherapy Dose Expansion
Arm group label:
Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab
Arm group label:
Phase 1b: Cohort C1 LOXO-435 Monotherapy Dose Expansion
Other name:
LY3866288
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
IV
Arm group label:
Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab
Other name:
KEYTRUDA®
Summary:
The main purpose of this study is to learn more about the safety, side effects, and
effectiveness of LOXO-435. LOXO-435 may be used to treat cancer of the cells that line
the urinary system and other solid tumor cancers that have a change in a particular gene
(known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and
possibly longer if the disease does not get worse.
Detailed description:
This is an open-label, multi-center, phase 1a/b study in participants with FGFR3-altered
advanced solid tumors, including metastatic urothelial cancer (UC). The study will be
conducted in 2 phases: Dose escalation and dose optimization (1a) and dose expansion
(1b). Phase 1a will include up to 2 cohorts to assess safety, tolerability, and
pharmacokinetics of LOXO-435 to determine the recommended phase 2 dose (RP2D) (or optimal
dose). Phase 1b will include 4 dose expansion cohorts of participants with prespecified
activating FGFR3 alterations to evaluate the efficacy and safety of LOXO-435 at the RP2D.
Cohort B will enroll pts with metastatic UC and includes three cohorts to evaluate
LOXO-435 as monotherapy (B1, B2) and in combination with pembrolizumab (B3). Cohort C
will enroll pts with non-UC advanced solid tumors and includes a cohort to evaluate
LOXO-435 as monotherapy (C1).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in
tumor or blood sample that is deemed as actionable.
- Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
- Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC)
that is locally advanced or metastatic with a qualifying FGFR3 alteration.
- Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial
cancer that is locally advanced or metastatic with a prespecified activating
FGFR3 alteration.
- Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial
solid tumor malignancy that is locally advanced or metastatic with a
prespecified activating FGFR3 alteration.
- Measurability of disease:
- Cohort A1: Measurable or non-measurable disease as defined by Response
Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
- Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by
RECIST v1.1
- Have adequate archival tumor tissue sample available or undergo a screening biopsy
if allowed per country-specific regulations.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Prior Systemic Therapy Criteria:
- Cohort A1/C1: Participant has received all standard therapies for which the
participant was deemed to be an appropriate candidate by the treating
Investigator; OR the participant is refusing the remaining most appropriate
standard of care treatment; OR there is no standard therapy available for the
disease. There is no restriction on number of prior therapies.
- Cohort A2/B1/B2/B3: Participants must have received at least one prior regimen
in the advanced or metastatic setting. There is no restriction on number of
prior therapies.
- FGFR inhibitor specific requirements:
- Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
- Cohort B1: Participants must have been previously treated with a FGFR
inhibitor.
- Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.
Exclusion Criteria:
- Participants with primary central nervous system (CNS) malignancy.
- Known or suspected history of uncontrolled CNS metastases.
- Current evidence of corneal keratopathy or retinal disorder.
- Have a history and/or current evidence of extensive tissue calcification.
- Any serious unresolved toxicities from prior therapy.
- Significant cardiovascular disease.
- Prolongation of the QT interval corrected for heart rate using Fridericia's formula
(QTcF).
- Active uncontrolled systemic infection or other clinically significant medical
conditions.
- Participants who are pregnant, lactating, or plan to breastfeed during the study or
within 6 months of the last dose of study treatment. Participants who have stopped
breastfeeding may be enrolled.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Facility:
Name:
UCLA Department of Medicine-Hematology/Oncology
Address:
City:
Santa Monica
Zip:
90095
Country:
United States
Status:
Recruiting
Facility:
Name:
Advent Health Hematology and Oncology
Address:
City:
Celebration
Zip:
34747
Country:
United States
Status:
Recruiting
Facility:
Name:
Winship Cancer Institute, Emory University
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Recruiting
Facility:
Name:
The University of Chicago Medical Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Facility:
Name:
SKCCC at Johns Hopkins
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02144
Country:
United States
Status:
Recruiting
Facility:
Name:
Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Facility:
Name:
Laura and Isaac Perlmutter Cancer Center
Address:
City:
New York
Zip:
10016
Country:
United States
Status:
Recruiting
Facility:
Name:
Icahn School of Medicine at Mount Sinai
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Facility:
Name:
University of North Carolina at Chapel Hill
Address:
City:
Chapel Hill
Zip:
27599-7305
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Facility:
Name:
Penn Medicine: University of Pennsylvania Health System/Perelman Center for Advanced Medicine
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Pittsburgh Medical Center
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Facility:
Name:
Carolina Urologic Research Center
Address:
City:
Myrtle Beach
Zip:
29572
Country:
United States
Status:
Recruiting
Facility:
Name:
Tennessee Oncology PLLC
Address:
City:
Nashville
Zip:
37204
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Texas Southwestern Medical Center
Address:
City:
Dallas
Zip:
75390
Country:
United States
Status:
Recruiting
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030-4009
Country:
United States
Status:
Recruiting
Facility:
Name:
Huntsman Cancer Institute
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Facility:
Name:
Royal North Shore Hospital
Address:
City:
Saint Leonards
Zip:
2065
Country:
Australia
Status:
Recruiting
Facility:
Name:
Kinghorn Cancer Centre
Address:
City:
Darlinghurst
Zip:
NSW 2010
Country:
Australia
Status:
Recruiting
Facility:
Name:
British Columbia Cancer Agency
Address:
City:
Vancouver
Zip:
V5Z 4E6
Country:
Canada
Status:
Recruiting
Facility:
Name:
Princess Margaret Hospital
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Recruiting
Facility:
Name:
Beijing Cancer hospital
Address:
City:
Beijing
Zip:
100730
Country:
China
Status:
Recruiting
Facility:
Name:
Beijing Cancer hospital
Address:
City:
Haidian
Zip:
100142
Country:
China
Status:
Recruiting
Facility:
Name:
The First Affiliated Hospital of Xi'an Jiaotong University
Address:
City:
Xi'an
Zip:
710061
Country:
China
Status:
Recruiting
Facility:
Name:
Zhejiang Provincial People's Hospital
Address:
City:
Hangzhou
Zip:
310014
Country:
China
Status:
Recruiting
Facility:
Name:
Zhejiang University
Address:
City:
Hangzhou
Zip:
310016
Country:
China
Status:
Recruiting
Facility:
Name:
Renji Hospital Affliated to Shanghai Jiaotong University
Address:
City:
Shanghai
Zip:
200001
Country:
China
Status:
Recruiting
Facility:
Name:
Tianjin Medical University Cancer Institute & Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Recruiting
Facility:
Name:
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Recruiting
Facility:
Name:
Centre Leon Berard
Address:
City:
Lyon
Zip:
69008
Country:
France
Status:
Recruiting
Facility:
Name:
Klinikum rechts der Isar de Technischen Universitaet Muenchen
Address:
City:
München
Zip:
81675
Country:
Germany
Status:
Recruiting
Facility:
Name:
Universitaetsklinikum Tuebingen
Address:
City:
Tuebingen
Zip:
72076
Country:
Germany
Status:
Recruiting
Facility:
Name:
Sheba Medical Center
Address:
City:
HaMerkaz
Zip:
5262100
Country:
Israel
Status:
Recruiting
Facility:
Name:
IRCCS Ospedale San Raffaele
Address:
City:
Milano
Zip:
20132
Country:
Italy
Status:
Recruiting
Facility:
Name:
Aichi Cancer Center Hospital
Address:
City:
Nagoya
Zip:
464-8681
Country:
Japan
Status:
Recruiting
Facility:
Name:
National Cancer Center Hospital
Address:
City:
Chuo Ku
Zip:
104-0045
Country:
Japan
Status:
Recruiting
Facility:
Name:
National Cancer Center Hospital East
Address:
City:
Chiba
Zip:
277-8577
Country:
Japan
Status:
Recruiting
Facility:
Name:
The Cancer Institute Hospital of JFCR
Address:
City:
Tokyo
Zip:
135-8550
Country:
Japan
Status:
Recruiting
Facility:
Name:
Asan Medical Center
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Seoul National University Hospital
Address:
City:
Seoul
Zip:
03080
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Severance Hospital, Yonsei University Health System
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Samsung Medical Center
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Erasmus Medisch Centrum
Address:
City:
Rotterdam
Zip:
3015 GD
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
Oslo University Hospital Ullevaal
Address:
City:
Oslo
Zip:
0379
Country:
Norway
Status:
Recruiting
Facility:
Name:
Haukeland University
Address:
City:
Bergen
Zip:
5021
Country:
Norway
Status:
Recruiting
Facility:
Name:
Centro Oncológico MD Anderson
Address:
City:
Madrid
Zip:
28033
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Facility:
Name:
START Madrid-CIOCC Loc. 1
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Marques de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Status:
Recruiting
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Start date:
January 12, 2023
Completion date:
June 2025
Lead sponsor:
Agency:
Eli Lilly and Company
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Eli Lilly and Company
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05614739
https://trials.lilly.com/en-US/trial/367675
