Neoplasm Metastasis Clinical Trial
Official title:
An Open-Label, Multicenter Study of LOXO-435 (LY3866288) In Advanced Solid Tumor Malignancies With FGFR3 Alterations
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Eli Lilly and Company | Loxo Oncology, Inc., Merck Sharp & Dohme LLC |
United States, Australia, Canada, China, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Norway, Spain, United Kingdom,
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 |
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