The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. 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.
This is an open-label, multi-center, phase 1 study in participants with FGFR3-altered advanced solid tumor malignancy including metastatic urothelial cancer (UC). The study will be conducted in 2 phases: Phase 1a dose escalation (Cohort A1) and dose optimization (Cohort A2) and Phase 1b dose expansion. Phase 1a will assess safety, tolerability, and pharmacokinetics of LOXO-435 to determine the optimal dose for further expansion. Phase 1b will include 6 dose expansion cohorts to evaluate the efficacy and safety of LOXO-435 as monotherapy or in combinations with pembrolizumab with or without enfortumab vedotin.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
535
University of Arizona - Cancer Center
Tucson, Arizona, United States
RECRUITINGCity of Hope
Duarte, California, United States
RECRUITINGUniversity of California, Los Angeles (UCLA) - Division of Hematology-Oncology
Los Angeles, California, United States
RECRUITINGUniversity of California - Irvine
Orange, California, United States
Phase 1a: To determine the recommended dose of LOXO-435: Safety, number of participants with dose-limiting toxicities (DLTs)
Number of participants with DLTs
Time frame: Minimum of the first 21-day cycle of LOXO-435 treatment
Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR)
ORR per investigator assessed RECIST v1.1
Time frame: Up to approximately 30 months or 2.5 years
Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
A summary of TEAEs and SAEs regardless of causality, will be reported in the Reported Adverse Events module
Time frame: Up to approximately 30 months or 2.5 years
To assess the pharmacokinetics (PK) of LOXO-435: Area under the concentration versus time curve (AUC)
PK of LOXO-435: AUC
Time frame: Up to 2 months
To assess the PK of LOXO-435: Minimum plasma concentration (Cmin)
PK of LOXO-435: Cmin
Time frame: Up to 2 months
To evaluate the preliminary antitumor activity of LOXO-435: Objective response rate (ORR)
ORR per investigator assessed RECIST 1.1
Time frame: Up to approximately 30 months or 2.5 years]
To evaluate the preliminary antitumor activity of LOXO-435: Duration of response (DoR)
DOR per investigator assessed RECIST 1.1
Time frame: Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Time to response (TTR)
TTR
Time frame: Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Progression-free survival (PFS)
PFS per investigator assessed RECIST 1.1
Time frame: Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Disease control rate (DCR)
DCR per investigator assessed RECIST 1.1
Time frame: Up to approximately 30 months or 2.5 years
To evaluate the preliminary antitumor activity of LOXO-435: Overall survival (OS)
OS
Time frame: Up to approximately 30 months or 2.5 years
Change from baseline in bladder-related symptoms, measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) subscale (BlCS)
The BlCS has 12 items with a total score range of 0 to 48, with higher scores representing better bladder-related symptoms. A ≥ 4-point score change from baseline will be considered as clinically meaningful improvement in bladder-related symptoms
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 day cycles)
Change from baseline in physical function, measured by FACT- Physical Well-being Scale (PWB) subscale
The PWB subscale has 7 items with a total score range of 0-28, with higher scores representing better physical function. A ≥ 3-point score change from baseline for a participant will be considered as clinically meaningful improvement in physical function.
Time frame: Up to approximately 30 months or 2.5 years
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACT
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CONTACT
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University of California (UC) Davis Comprehensive Cancer Center
Sacramento, California, United States
RECRUITINGStanford Cancer Center
Stanford, California, United States
RECRUITINGAdvent Health
Orlando, Florida, United States
RECRUITINGEmory University Hospital
Atlanta, Georgia, United States
RECRUITINGThe University of Chicago Medical Center (UCMC)
Chicago, Illinois, United States
RECRUITINGIndiana University (IU) Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
RECRUITING...and 74 more locations