Phase 1 study for people with Bladder Cancer

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria:

• Cohort A1, C1, D1, and D2: Locally advanced or metastatic solid tumor malignancy with a qualifying FGFR3 alteration.

• Cohort A2, B2, B5 and B7: Urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration.

• Cohorts B1 and B4: Urothelial cancer that is locally advanced or metastatic and have received prior erdafitinib.

• Cohort B6: Muscle Invasive Bladder Cancer with a qualifying FGFR3 alteration.

• Cohort B7: Urothelial cancer that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration and expression of human epidermal growth factor receptor 2 (HER2).

• Cohort B8: Low Grade Intermediate Risk Non-Muscle Invasive Bladder cancer and a qualifying FGFR3 genetic alteration.

• Measurability of disease:

  • Cohort A1, D1, and D2: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1).
  • Cohorts A2, B1, B2, B4, B5, B7, and C1: Measurable disease required as defined by RECIST v1.1.
  • Cohort B8: Baseline disease which includes at least 1 lesion.

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of:

  • 0 or 1 for Cohorts A1, A2, B5, B6, B7, and B8.
  • Less than or equal to 2 for Cohorts B1, B2, B4, C1, DI and D2.

• Cohort B6: Must be eligible for radical cystectomy plus pelvic lymph node dissection and agree to undergo curative intent standard radical cystectomy plus pelvic lymph node dissection.

Exclusion Criteria:

• Participants with primary central nervous system (CNS) malignancy.

• Untreated or uncontrolled CNS metastases.

• Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic 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 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.

• Cohort D1 only:

  • Have had renal transplantation.
  • Have a known history of nephrotic syndrome.
  • Have uncontrolled fluid overload, including clinically significant ascites, pleural effusion, or peripheral edema.
  • Have uncontrolled hypertension.
  • Are on hemodialysis or similar.

• Cohort D2 only:

  • Have a history of:
  • Ventricular tachycardia or ventricular fibrillation.
  • Hypertrophic obstructive cardiomyopathy unless managed concurrently with atrial fibrillation.
  • Wolff-Parkinson-White syndrome.
  • Second- or third-degree atrioventricular block unless a functioning pacemaker is in place.
  • Heart rate less than (<) 50 bpm.
  • Have any of these medical conditions:
  • Severe respiratory insufficiency.
  • Sleep apnea syndrome.
  • Myasthenia gravis.
  • Acute narrow-angle glaucoma.
  • Active liver disease or clinically significant hepatic impairment.
  • History of myopathy or rhabdomyolysis with any HMG-CoA reductase inhibitor.