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

An Open-label, Phase 1 Study of KHK2455 in Combination With Avelumab in Adult Subjects With Locally Advanced or Metastatic Urothelial Carcinoma

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).

Study Overview

• Status: Terminated
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: KHK2455; Drug: Avelumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Kyowa Research Site ESP002
  • Barcelona, Spain, 08035
    • Kyowa Research Site ESP003
  • Madrid, Spain, 28040
    • Kyowa Research Site ESP004
  • Madrid, Spain, 28050
    • Kyowa Research Site ESP001
• United States
  • Florida
    • Saint Petersburg, Florida, United States, 33709
      • Kyowa Research Site USA001
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Kyowa Research Site USA005
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Kyowa Research Site USA006
  • Texas
    • Houston, Texas, United States, 77030
      • Kyowa Research Site USA 009
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Kyowa Research Site USA007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KHK2455 in Combination with Avelumab	Drug: KHK2455; orally, once daily.; Drug: Avelumab; IV Administration; Other Names: Bavencio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0	To characterize the safety and tolerability of KHK2455 administered in combination with avelumab in subjects with locally advanced or metastatic urothelial carcinoma (including bladder, urethra, ureters, and renal pelvis).	up to 24 months

Collaborators and Investigators

• Sponsor: Kyowa Kirin, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2019
• Primary Completion (Actual): November 15, 2022
• Study Completion (Actual): November 15, 2022

Study Registration Dates

• First Submitted: March 19, 2019
• First Submitted That Met QC Criteria: April 11, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: 2455-002; 2018-003796-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No