KHK2455 (IDO Inhibitor) Plus Avelumab in Adult Subjects With Advanced Bladder Cancer

Status: Active

Description

This is a two-part (dose-escalation, dose-expansion), multicenter, open-label Phase 1 study of KHK2455 in combination with avelumab in adult subjects with locally advanced or metastatic urothelial carcinoma (including bladder, urethra, ureters, and renal pelvis).

Eligibility Criteria

Inclusion Criteria

  • Subjects may be male or female and must be ≥ 18 years of age; have an ECOG PS of 0 or 1; and a life expectancy of > 3 months in the Investigator's judgment;
  • Subjects are able to understand and willing to sign the ICF, according to institutional standards, prior to the initiation of any study related procedures
  • Subjects must have histological or cytological evidence of metastatic or advanced urothelial carcinoma (including bladder, urethra, ureters, and renal pelvis that has predominantly transitional cell or urothelial features); and have measurable neoplastic disease according to RECIST v1.1 criteria
  • Subjects must have been previously treated with a platinum-based therapy and progressed during or within 12 months of treatment; and be checkpoint-inhibitor naive (not treated with agents targeting PD-1, PD-L1 or CTLA-4)
  • Subjects must have a tumor accessible for fresh biopsy at the baseline visit and for subsequent biopsies during the study for IDO assessment. Archived tissue from previous biopsies (formalin fixed-paraffin embedded [FFPE] block of <12 months) are permitted for PD-L1 analysis
  • Subjects must be able to swallow the solid (encapsulated) dosage form of KHK2455

Exclusion Criteria

  • Subjects who have been previously treated with avelumab or any IDO1 inhibitor or CTLA-4, PD-1/PD-L1 checkpoint inhibitors; or any investigational immunotherapy including but not limited to anti-cancer vaccines or oncotropic viruses
  • Subjects with liver and/or bone metastases;
  • Subjects with a history of organ transplant or allogeneic bone marrow transplant;
  • Subjects with pre-existing uveitis or other known clinically meaningful retinal disorders as determined by a local ophthalmologist

Locations & Contacts

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: In review
Name Not Available

Trial Objectives and Outline

This is a two-part (dose-escalation, dose-expansion), multicenter, open-label Phase 1 study of KHK2455 in combination with avelumab in adult subjects with locally advanced or metastatic urothelial carcinoma (including bladder, urethra, ureters, and renal pelvis). Subjects will be screened for entry into this study after signing informed consent. Subjects must meet inclusion/exclusion criteria to participate in this study. - Part 1 (dose-escalation phase) has has a 3+3 design that will evaluate the safety and tolerability and identify the MTD or highest protocol-defined dose, in the absence of exceeding the MTD. - Part 2 (cohort-expansion phase) will further explore the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity for the combination regimen at the MTD or highest dose level tested.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Kyowa Kirin Pharmaceutical Development, Inc.

Trial IDs

Primary ID 2455-002
Secondary IDs NCI-2019-04161
Clinicaltrials.gov ID NCT03915405