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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: 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)

Primary Outcome 1 - Timeframe: During the first 21-day cycle of LOXO-435 treatment

Primary Outcome 2 - Measure: Phase 1b: To evaluate the preliminary antitumor activity of LOXO-435: Overall response rate (ORR)

Primary Outcome 2 - Timeframe: Up to approximately 30 months or 2.5 years

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 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.
Exclusion 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

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: Ryan Widau, PhD

Phone: 855-569-6305

Email: clinicaltrials@loxooncology.com

LOCATION