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

JRCT ID: jRCT2031230098

Registered date:26/05/2023

Basic Information

• Recruitment status: Recruiting

Health condition(s) or Problem(s) studied

Urinary Bladder Neoplasms
Neoplasm Metastasis
Ureteral Neoplasms

• Date of first enrollment: 05/07/2023
• Target sample size: 140
• Countries of recruitment: United States,Japan,Australia,Japan
• Study type: Interventional

Intervention(s)

Drug: LOXO-435
Oral
Other Name: LY3866288
Drug: Pembrolizumab
IV

Study Arms
Experimental: Phase 1a: LOXO-435 Monotherapy Dose Escalation
LOXO-435 administered orally to participants with FGFR3-altered advanced solid tumors.
Intervention: Drug: LOXO-435
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.
Intervention: Drug: LOXO-435
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.
Intervention: Drug: LOXO-435
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.
Interventions:
Drug: LOXO-435
Drug: Pembrolizumab
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.
Intervention: Drug: LOXO-435

Outcome(s)

Primary Outcome

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

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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 naive.

Exclude criteria

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

Related Information

• Primary Sponsor: Masaki Takeshi
• Secondary ID(s): NCT05614739