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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05614739




Registration number
NCT05614739
Ethics application status
Date submitted
7/11/2022
Date registered
14/11/2022

Titles & IDs
Public title
A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
Scientific title
An Open-Label, Multicenter Study of LOXO-435 (LY3866288) In Advanced Solid Tumor Malignancies With FGFR3 Alterations
Secondary ID [1] 0 0
J4G-OX-JZVA
Secondary ID [2] 0 0
LOXO-FG3-22001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Urinary Bladder Neoplasms 0 0
Neoplasm Metastasis 0 0
Ureteral Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bladder - transitional cell cancer
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LOXO-435
Treatment: Drugs - Pembrolizumab

Experimental: Phase 1a: Cohort A1 LOXO-435 Monotherapy Dose Escalation - LOXO-435 administered orally to participants with FGFR3-altered advanced solid tumors.

Experimental: Phase 1a: Cohort A2 LOXO-435 Monotherapy Dose Optimization - LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma. (Cohort to be implemented as needed, based on Sponsor's discretion.)

Experimental: Phase 1b: Cohort B1 LOXO-435 Monotherapy Dose Expansion - LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma who were previously treated with an FGFR inhibitor.

Experimental: Phase 1b: Cohort B2 LOXO-435 Monotherapy Dose Expansion - LOXO-435 administered orally to participants with FGFR3-altered advanced urothelial carcinoma who have not received a prior FGFR inhibitor.

Experimental: Phase 1b: Cohort B3 LOXO-435 Plus Pembrolizumab - LOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV) to participants with FGFR3-altered advanced urothelial carcinoma who have not received a prior FGFR inhibitor.

Experimental: Phase 1b: Cohort C1 LOXO-435 Monotherapy Dose Expansion - LOXO-435 administered orally to participants with advanced solid tumors who have not received a prior FGFR inhibitor.


Treatment: Drugs: LOXO-435
Oral

Treatment: Drugs: Pembrolizumab
IV

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: To determine the recommended phase 2 dose (RP2D)/optimal dose of LOXO-435: Safety, number of participants with dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Minimum of the first 21-day cycle of LOXO-435 treatment
Primary outcome [2] 0 0
Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR)
Timepoint [2] 0 0
Up to approximately 30 months or 2.5 years
Secondary outcome [1] 0 0
To assess the pharmacokinetics (PK) of LOXO-435: Area under the concentration versus time curve (AUC)
Timepoint [1] 0 0
Up to 2 months
Secondary outcome [2] 0 0
To assess the PK of LOXO-435: Minimum plasma concentration (Cmin)
Timepoint [2] 0 0
Up to 2 months
Secondary outcome [3] 0 0
To evaluate the preliminary antitumor activity of LOXO-435: Duration of response (DoR)
Timepoint [3] 0 0
Up to approximately 30 months or 2.5 years
Secondary outcome [4] 0 0
To evaluate the preliminary antitumor activity of LOXO-435: Time to response (TTR)
Timepoint [4] 0 0
Up to approximately 30 months or 2.5 years
Secondary outcome [5] 0 0
To evaluate the preliminary antitumor activity of LOXO-435: Progression-free survival (PFS)
Timepoint [5] 0 0
Up to approximately 30 months or 2.5 years
Secondary outcome [6] 0 0
To evaluate the preliminary antitumor activity of LOXO-435: Disease control rate (DCR)
Timepoint [6] 0 0
Up to approximately 30 months or 2.5 years
Secondary outcome [7] 0 0
To evaluate the preliminary antitumor activity of LOXO-435: Overall survival (OS)
Timepoint [7] 0 0
Up to approximately 30 months or 2.5 years
Secondary outcome [8] 0 0
Change from baseline in bladder-related symptoms, measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) subscale (BlCS)
Timepoint [8] 0 0
Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 day cycles)
Secondary outcome [9] 0 0
Change from baseline in physical function, measured by FACT- Physical Well-being Scale (PWB) subscale
Timepoint [9] 0 0
Up to approximately 30 months or 2.5 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
Kinghorn Cancer Centre - Darlinghurst
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
NSW 2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Utah
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
China
State/province [19] 0 0
Beijing
Country [20] 0 0
China
State/province [20] 0 0
Shanxi
Country [21] 0 0
China
State/province [21] 0 0
Zhejiang
Country [22] 0 0
China
State/province [22] 0 0
Shanghai
Country [23] 0 0
China
State/province [23] 0 0
Tianjin
Country [24] 0 0
France
State/province [24] 0 0
Aquitaine
Country [25] 0 0
France
State/province [25] 0 0
Lyon
Country [26] 0 0
France
State/province [26] 0 0
Villejuif Cedex
Country [27] 0 0
Germany
State/province [27] 0 0
München
Country [28] 0 0
Germany
State/province [28] 0 0
Tuebingen
Country [29] 0 0
Israel
State/province [29] 0 0
HaMerkaz
Country [30] 0 0
Italy
State/province [30] 0 0
Milan
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
Japan
State/province [32] 0 0
Aichi
Country [33] 0 0
Japan
State/province [33] 0 0
Tokyo
Country [34] 0 0
Japan
State/province [34] 0 0
Chiba
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul]
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Seoul
Country [37] 0 0
Netherlands
State/province [37] 0 0
Zuid-Holland
Country [38] 0 0
Norway
State/province [38] 0 0
Roma
Country [39] 0 0
Norway
State/province [39] 0 0
Bergen
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Santander
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ryan Widau, PhD
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Address 0 0
Country 0 0
Phone 0 0
13176154559
Fax 0 0
Email 0 0
ClinicalTrials.gov@lilly.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.