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

• ClinicalTrials.gov Identifier: NCT03915405
• Recruitment Status: Recruiting
• First Posted: April 16, 2019
• Last Update Posted: July 10, 2020
• Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.
• Information provided by (Responsible Party): Kyowa Kirin Pharmaceutical Development, Inc.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Urothelial Carcinoma	Drug: KHK2455; Drug: Avelumab	Phase 1

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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Phase 1 Study of KHK2455 in Combination With Avelumab in Adult Subjects With Locally Advanced or Metastatic Urothelial Carcinoma
• Actual Study Start Date: September 26, 2019
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: February 25, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: KHK2455 in Combination with Avelumab	Drug: KHK2455; orally, once daily.; Drug: Avelumab; IV Administration

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0 [ Time Frame: up to 24 months ]
   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).

Eligibility Criteria

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

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 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

Contacts and Locations

Contacts

Contact: Kyowa Kirin Pharmaceutical Development, Inc.; 1-609-919-1100; KKD.clinical.info@kyowakirin.com

Locations

United States, Arizona

Kyowa Research Site USA004; Recruiting

Gilbert, Arizona, United States, 85234

United States, Florida

Kyowa Research Site USA001; Recruiting

Saint Petersburg, Florida, United States, 33709

United States, Iowa

Kyowa Research Site USA005; Recruiting

Iowa City, Iowa, United States, 52242

Spain

Kyowa Research Site ESP002; Recruiting

Barcelona, Spain, 08003

Kyowa Research Site ESP003; Recruiting

Barcelona, Spain, 08035

Kyowa Research Site ESP004; Recruiting

Madrid, Spain, 28040

Kyowa Research Site ESP001; Recruiting

Madrid, Spain, 28050

Sponsors and Collaborators

Kyowa Kirin Pharmaceutical Development, Inc.

More Information

• Responsible Party: Kyowa Kirin Pharmaceutical Development, Inc.
• ClinicalTrials.gov Identifier: NCT03915405
• Other Study ID Numbers: 2455-002
• First Posted: April 16, 2019
• Last Update Posted: July 10, 2020
• Last Verified: July 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Transitional Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms