Bacillus Calmette-Guérin and Eciskafusp alfa combination (BCG + N-803)

The combination of Bacillus Calmette-Guérin (BCG) and eciskafusp alfa (also known as N-803 or nogapendekin alfa inbakicept) is a synergistic immunotherapy regimen designed for the treatment of bladder cancer. BCG is a live-attenuated bacterial vaccine that, when administered intravesically, induces a local innate immune response and recruits inflammatory cells to the bladder wall [1]. Eciskafusp alfa is an interleukin-15 (IL-15) superagonist complex that specifically targets the IL-15 receptor beta-gamma (IL-15Rβγ) on natural killer (NK) cells and CD8+ T cells, promoting their proliferation and activation without stimulating regulatory T cells [2]. By combining these two agents, the regimen enhances the recruitment and cytotoxic activity of effector immune cells within the tumor microenvironment, effectively overcoming resistance in patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) [3]. This combination was approved by the FDA in 2024 for patients with NMIBC with carcinoma in situ (CIS) who have failed prior BCG therapy [1]. Clinical data from the QUILT-3.032 trial demonstrated high complete response rates and durable efficacy, marking a significant advancement in the management of high-risk bladder cancer [4].

Other names

N-803ALT-803AnktivaNogapendekin alfa inbakicept-pmlnBCG plus N-803BCG plus eciskafusp alfa

The combination works through a dual-mechanism of immune stimulation: BCG induces a local inflammatory response and recruits immune cells via Toll-like receptor (TLR) signaling, while eciskafusp alfa (N-803) acts as an IL-15 superagonist to drive the expansion and activation of cytotoxic NK cells and CD8+ T cells [1, 2, 4].