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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05614739




Registration number
NCT05614739
Ethics application status
Date submitted
7/11/2022
Date registered
14/11/2022
Date last updated
23/05/2024

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
12/01/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2025
Actual
Sample size
Target
180
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
Kinghorn Cancer Centre - Darlinghurst
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 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
Guangdong
Country [21] 0 0
China
State/province [21] 0 0
Shanghai
Country [22] 0 0
China
State/province [22] 0 0
Shanxi
Country [23] 0 0
China
State/province [23] 0 0
Zhejiang
Country [24] 0 0
France
State/province [24] 0 0
Aquitaine
Country [25] 0 0
France
State/province [25] 0 0
Shanxi
Country [26] 0 0
France
State/province [26] 0 0
Lyon
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
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Sheffield

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
Loxo Oncology, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Merck Sharp & Dohme LLC
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05614739
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ryan Widau, PhD
Address 0 0
Loxo Oncology, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Patient Advocacy
Address 0 0
Country 0 0
Phone 0 0
855-569-6305
Fax 0 0
Email 0 0
clinicaltrials@loxooncology.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05614739