A phase 1 study of IO102-IO103 vaccine plus pembrolizumab in patients with BCG-intolerant or unresponsive non-muscle invasive bladder cancer (NMIBC).

Abstract

TPS716 Background: Pembrolizumab, an anti-PD1 antibody, is a treatment option for high-risk BCG-unresponsive NMIBC, but has a modest complete response (CR) rate of 41% at 3 months, and a median duration of CR of 16.2 months. IO102-IO103 is a novel immune-modulating cancer vaccine that stimulates activation of T cells targeting indoleamine-2,3-dioxygenase 1 (IDO1) and PDL1-positive cells, resulting in potentially increased susceptibility to anti-PD-1 blockade. Combination IO102-IO103 with nivolumab showed encouraging clinical activity and tolerability in previously anti-PD-1 naïve metastatic melanoma patients (NCT03047928). The existing data for synergistic effects of IO102-IO103 in combination with anti-PD1 therapy and the known expression of IDO in urothelial carcinoma lend rationale to this phase I trial designed to assess the feasibility, safety, and toxicity of IO102-IO103 plus pembrolizumab in patients with BCG-intolerant or unresponsive NMIBC. Methods: This open-label, single arm, phase 1 study enrolls patients with BCG-unresponsive or intolerant high-risk NMIBC who are ineligible for or have declined cystectomy and have adequate ECOG performance status (0-2), hematologic function, and end organ function. High-risk NMIBC is defined as T1, high-grade Ta, or CIS/Tis, with predominantly urothelial cell histology. Exclusion criteria include known active autoimmune disorders requiring immunosuppressive therapy or prior checkpoint inhibitor therapy. Eligible patients will be treated with pembrolizumab 200 mg IV on Day (D) 1, and IO102-IO103 85 mcg SQ on D1 and 8 of a 21-day cycle for the first two cycles, after which IO102-IO103 dosing will be D1 only, with treatment for up to 2 years. The primary endpoints of feasibility, safety, and toxicity will be evaluated by CTCAE v5.0 criteria and will be met if ≥10 patients out of 12 are able to complete the first cycle without experiencing pre-specified treatment-limiting toxicities. Key secondary endpoints include CR rate at 3 months, median duration of response, and cystectomy-free survival at 18 months. Biopsy specimens and serial urine and blood samples will be collected to evaluate potential biomarkers of response. Clinical trial information: NCT05843448 .