FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3

Inclusion Criteria:

• Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing intumor or blood sample that is deemed as actionable

• Cohort A1: Presence of an alteration in FGFR3 or its ligands

• Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC)that is locally advanced or metastatic with a qualifying FGFR3 geneticalteration

• Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locallyadvanced or metastatic

• Cohort C1: Must have histological diagnosis of a non-urothelial solid tumormalignancy that is locally advanced or metastatic with a qualifying FGFR3genetic alteration

• Measurability of disease:

• Cohort A1 and B3: Measurable or non-measurable disease as defined by ResponseEvaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)

• Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined byRECIST v1.1

• Have adequate tumor tissue sample available. Participants with inadequate tissuesample availability may still be considered for enrollment upon review

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 forCohorts A1, A2, B3, and B5

• Less than or equal to 2 for Cohorts B1, B2, B4, and C1

• Prior Systemic Therapy Criteria:

• Cohort A1/C1: Participant has received all standard therapies for which theparticipant was deemed to be an appropriate candidate by the treatingInvestigator; OR the participant is refusing the remaining most appropriatestandard of care treatment; OR there is no standard therapy available for thedisease. There is no restriction on number of prior therapies.

• Cohort A2, B2, B3 participants must have received at least one prior regimen,and cohorts B1 and B4 participants at least 2 prior regimens, in the locallyadvanced or metastatic setting

• There is no restriction on number of prior therapies

• Cohort B5: Participants have not received prior systemic therapy for locallyadvanced or metastatic UC

• FGFR inhibitor specific requirements:

• Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required

• Cohort B1/B4: Participants must have been previously treated with erdafitinib

• Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve

Exclusion Criteria:

• Participants with primary central nervous system (CNS) malignancy

• Untreated or uncontrolled CNS metastases

• Current evidence of corneal keratopathy or retinal disorder. Individuals withasymptomatic ophthalmic conditions may be eligible

• 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 medicalconditions

• Participants who are pregnant, lactating, or plan to breastfeed during the study orwithin 6 months of the last dose of study treatment. Participants who have stoppedbreastfeeding may be enrolled