A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3

Neoplasm Metastasis Clinical Trial

Official title:

An Open-Label, Multicenter Study of LOXO-435 (LY3866288) In Advanced Solid Tumor Malignancies With FGFR3 Alterations

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05614739
• Other study ID #: LOXO-FG3-22001
• Secondary ID: J4G-OX-JZVA2022-
• Status: Recruiting
• Phase: Phase 1
• Start date: January 12, 2023
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: Patient Advocacy
• Phone: 855-569-6305
• Email: clinicaltrials[@]loxooncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Neoplasms
• Ureteral Neoplasms
• Urinary Bladder Neoplasms

Intervention

Drug:
• LOXO-435
Oral
• Pembrolizumab
IV

Locations

Country	Name	City	State
Australia	Kinghorn Cancer Centre	Darlinghurst
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
China	Beijing Cancer hospital	Beijing	Beijing
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Beijing Cancer hospital	Haidian	Beijing
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Zhejiang University	Hangzhou	Zhejiang
China	Renji Hospital Affliated to Shanghai Jiaotong University	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Zhejiang
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
France	Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux	Aquitaine
France	Centre Leon Berard	Lyon
France	Gustave Roussy	Villejuif	Shanxi
Germany	Klinikum rechts der Isar de Technischen Universitaet Muenchen	München
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Israel	Beilinson Hospital	Petach Tikva	HaMerkaz
Israel	Sheba Medical Center	Ramat Gan	HaMerkaz
Italy	IRCCS Ospedale San Raffaele	Milano	Milan
Italy	UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore	Roma
Japan	National Cancer Center Hospital East	Chiba
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Korea, Republic of	Asan Medical Center	Seoul	Seoul]
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Netherlands	Erasmus Medisch Centrum	Rotterdam	Zuid-Holland
Norway	Haukeland University	Bergen
Norway	Oslo University Hospital Ullevaal	Oslo	Roma
Spain	Institut Catala d'Oncologia L'Hospitalet	Barcelona
Spain	Centro Oncológico MD Anderson	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	South Texas Accelerated Research Therapeutics (START) Madrid	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	SKCCC at Johns Hopkins	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Advent Health Hematology and Oncology	Celebration	Florida
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Medical Center	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Laura and Isaac Perlmutter Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Penn Medicine: University of Pennsylvania Health System/Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCLA Department of Medicine-Hematology/Oncology	Santa Monica	California

Sponsors (3)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc., Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: To determine the recommended phase 2 dose (RP2D)/optimal dose of LOXO-435: Safety, number of participants with dose-limiting toxicities (DLTs)	Number of participants with DLTs	Minimum of the first 21-day cycle of LOXO-435 treatment
Primary	Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR)	ORR per investigator assessed RECIST v1.1	Up to approximately 30 months or 2.5 years
Secondary	To assess the pharmacokinetics (PK) of LOXO-435: Area under the concentration versus time curve (AUC)	PK of LOXO-435: AUC	Up to 2 months
Secondary	To assess the PK of LOXO-435: Minimum plasma concentration (Cmin)	PK of LOXO-435: Cmin	Up to 2 months
Secondary	To evaluate the preliminary antitumor activity of LOXO-435: Duration of response (DoR)	DOR per investigator assessed RECIST 1.1	Up to approximately 30 months or 2.5 years
Secondary	To evaluate the preliminary antitumor activity of LOXO-435: Time to response (TTR)	TTR	Up to approximately 30 months or 2.5 years
Secondary	To evaluate the preliminary antitumor activity of LOXO-435: Progression-free survival (PFS)	PFS per investigator assessed RECIST 1.1	Up to approximately 30 months or 2.5 years
Secondary	To evaluate the preliminary antitumor activity of LOXO-435: Disease control rate (DCR)	DCR per investigator assessed RECIST 1.1	Up to approximately 30 months or 2.5 years
Secondary	To evaluate the preliminary antitumor activity of LOXO-435: Overall survival (OS)	OS	Up to approximately 30 months or 2.5 years
Secondary	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	Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 day cycles)
Secondary	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.	Up to approximately 30 months or 2.5 years

External Links

•   A Study of LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3