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

Kyowa Kirin

Status and phase

Terminated

Phase 1

Conditions

Urothelial Carcinoma

Treatments

Drug: Avelumab

Drug: KHK2455

Study type

Interventional

Funder types

Industry

Identifiers

NCT03915405

2455-002

2018-003796-35 (EudraCT Number)

Details and patient eligibility

About

Full 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). 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 a modified 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.

Enrollment

16 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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; OR Been previously treated with platinum based adjuvant or neo-adjuvant therapy and relapsed or progressed; OR
Be platinum-based chemotherapy intolerant or ineligible; OR
Have progressed during or after treatment with approved PD-1/PD-L1 inhibitors
Subjects must have a tumor accessible for fresh biopsy at the baseline visit and for IDO assessment. If current circumstances prohibit the biopsy procedure (e.g., temporary hospital protocol restrictions, regulatory or local authority requirements, etc.) then archived tissue from previous biopsies (fresh frozen tissue < 9 months and formalin fixed-paraffin embedded [FFPE] block of ≤ 24 months) without intervening checkpoint inhibitors can substitute for a fresh baseline biopsy;
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 prior or current liver 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