Brief Title: LOXO-435 in Patients With Cancer With a Change in a Gene Called FGFR3

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

• Urinary Bladder Neoplasms
• Neoplasm Metastasis
• Ureteral Neoplasms

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Ryan Widau, PhD

Role: Study Director

Affiliation: Loxo Oncology, Inc.

Overall Contact

Name: Patient Advocacy

Phone: 855-569-6305

Email: clinicaltrials@loxooncology.com

LOCATION