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).
Recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| KHK2455 | KHK2455 in Combination with Avelumab | |
| Avelumab | Bavencio | KHK2455 in Combination with Avelumab |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| KHK2455 in Combination with Avelumab | Experimental |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0 |
| Time Frame: | up to 24 months |
| Safety Issue: | |
| Description: | 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). |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Kyowa Kirin, Inc. |
April 30, 2021
