Promising efficacy and safety of feladilimab in recurrent/metastatic urothelial carcinoma

Results from the phase 1 INDUCE-1 trial showed promising activity and manageable safety of the ICOS agonist feladilimab as monotherapy or combined with pembrolizumab in patients with recurrent/metastatic urothelial carcinoma.

Inducible T-cell co-stimulator (ICOS) is a member of the CD23 receptor superfamily, which includes CTLA-4 and PD-1, and has a pivotal role in stimulating T-cell proliferation, differentiation, survival, and function [1]. ICOS is highly expressed in all stages of urothelial cancer.

The phase 1 INDUCE trial (NCT02723955) evaluates feladilimab as monotherapy and in combination with pembrolizumab in selected advanced solid tumours. Eligible patients had recurrent/metastatic urothelial carcinoma of the upper or lower urinary tract, 6 or fewer prior systemic therapy lines in the advanced setting, measurable disease, and no active autoimmune disease. Anti-PD-(L)1-experienced patients (n=14) received monotherapy feladilimab (0.3 mg/kg every 3 weeks), and anti-PD-(L)1-naïve patients (n=32) received feladilimab plus pembrolizumab (200 mg every 3 weeks) for up to 35 cycles until disease progression or unacceptable toxicity. Dr Arjun Balar (Perlmutter Cancer Center, NY, USA) presented preliminary results from the urothelial carcinoma expansion cohorts [2].

In the monotherapy arm, median duration of follow-up was 12.6 months; overall response rate was 7% (1 partial responder) with a duration of response of 6.1 months. Disease control rate was 21%, and median overall survival was 14.5 months, with 77% of patients alive at 6 months. In the combination arm, median duration of follow-up was 9.6 months; overall response rate was 22% (7 partial responders) with a median duration of response of 8.3 months. Disease control rate was 63%, and median overall survival was 10.7 months, with 64% of patients alive at 6 months.

Grade ≥3 treatment-related adverse events were reported for 0% and 9% of patients in the monotherapy arm and combination arm, respectively. A trend was observed for enrichment of clinical activity in patients with tumours expressing PD-L1, ICOS, or both.

1. Simpson TR, et al. Curr Opin Immunol. 201;22:326-332.
2. Balar AV, et al. Inducible T-cell co-stimulatory (ICOS) receptor agonist, feladilimab (fela), alone and in combination (combo) with pembrolizumab (P): Results from INDUCE-1 urothelial carcinoma (UC) expansion cohorts (ECs). Abstract 4519, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August, 202125 March, 2024