A Study of LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3
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|ClinicalTrials.gov Identifier: NCT05614739|
Recruitment Status : Recruiting
First Posted : November 14, 2022
Last Update Posted : June 2, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Urinary Bladder Neoplasms Neoplasm Metastasis Ureteral Neoplasms||Drug: LOXO-435 Drug: Pembrolizumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||140 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Multicenter Study of LOXO-435 (LY3866288) In Advanced Solid Tumor Malignancies With FGFR3 Alterations|
|Actual Study Start Date :||January 19, 2023|
|Estimated Primary Completion Date :||June 2025|
|Estimated Study Completion Date :||June 2025|
Experimental: Phase 1a: LOXO-435 Monotherapy Dose Escalation
LOXO-435 administered orally to participants with FGFR3-altered advanced solid tumors.
Other Name: LY3866288
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.
Other Name: LY3866288
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.
Other Name: LY3866288
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.
Other Name: LY3866288
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.
Other Name: LY3866288
- Phase 1a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-435: Number of patients with dose-limiting toxicities (DLTs) [ Time Frame: During the first 21-day cycle of LOXO-435 treatment ]Number of patients with DLTs
- Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR) [ Time Frame: Up to approximately 30 months or 2.5 years ]ORR per investigator assessed RECIST v1.1
- To assess the pharmacokinetics (PK) of LOXO-435: Area under the concentration versus time curve (AUC) [ Time Frame: Up to 2 months ]PK of LOXO-435: AUC
- To assess the PK of LOXO-435: Minimum plasma concentration (Cmin) [ Time Frame: Up to 2 months ]PK of LOXO-435: Cmin
- To evaluate the preliminary antitumor activity of LOXO-435: Duration of response (DoR) [ Time Frame: Up to approximately 30 months or 2.5 years ]DOR per investigator assessed RECIST 1.1
- To evaluate the preliminary antitumor activity of LOXO-435: Time to response (TTR) [ Time Frame: Up to approximately 30 months or 2.5 years ]TTR
- To evaluate the preliminary antitumor activity of LOXO-435: Progression-free survival (PFS) [ Time Frame: Up to approximately 30 months or 2.5 years ]PFS per investigator assessed RECIST 1.1
- To evaluate the preliminary antitumor activity of LOXO-435: Disease control rate (DCR) [ Time Frame: Up to approximately 30 months or 2.5 years ]DCR per investigator assessed RECIST 1.1
- To evaluate the preliminary antitumor activity of LOXO-435: Overall survival (OS) [ Time Frame: Up to approximately 30 months or 2.5 years ]OS
- Change from baseline in bladder-related symptoms, measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) subscale (BlCS) [ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 day cycles) ]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
- Change from baseline in physical function, measured by FACT- Physical Well-being Scale (PWB) subscale [ Time Frame: Up to approximately 30 months or 2.5 years ]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 patient will be considered as clinically meaningful improvement in physical function.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
- Cohort A (Dose Escalation): Presence of an alteration in FGFR3 or its ligands deemed as a clinically or potentially clinically relevant alteration by the treating Investigator.
- 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:
- Phase 1a: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
- Phase 1b: 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.
Patient has received all standard therapies for which the patient was deemed to be an appropriate candidate by the treating Investigator; OR the patient 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 B1: Patients must have been previously treated with a FGFR inhibitor.
- Cohort B2, B3, C1: Patients must be FGFR inhibitor naïve.
- Patients 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
- Patients who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05614739
|Contact: Patient Advocacyfirstname.lastname@example.org|
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|United States, North Carolina|
|University of North Carolina at Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27599-7305|
|United States, Pennsylvania|
|UPMC Hillman Cancer Center||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, South Carolina|
|Carolina Urologic Research Center||Recruiting|
|Myrtle Beach, South Carolina, United States, 29572|
|United States, Tennessee|
|Sarah Cannon and HCA Research Institute||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Kinghorn Cancer Centre||Recruiting|
|Darlinghurst, Australia, NSW 2010|
|Aichi Cancer Center Hospital||Recruiting|
|Nagoya, Aichi, Japan, 464-8681|
|Study Director:||Ryan Widau, PhD||Loxo Oncology, Inc.|
|Responsible Party:||Eli Lilly and Company|
|Other Study ID Numbers:||
J4G-OX-JZVA ( Other Identifier: Eli Lilly and Company )
2022-502755-59-00 ( Other Identifier: EU CTR # )
|First Posted:||November 14, 2022 Key Record Dates|
|Last Update Posted:||June 2, 2023|
|Last Verified:||June 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Bladder Urothelial Carcinoma
Urinary Bladder Cancer
Urinary Tract Cancer
Renal Pelvis Cancer
Urinary Bladder Neoplasms
Neoplasms by Site
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urinary Bladder Diseases
Male Urogenital Diseases
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action