Updated results on multiple antigens stimulating cellular therapy (MASCT-I) in metastatic urothelial carcinoma: A randomized, open-label, phase I trial.
Authors: Shi Yanxia , Chen Meiting , An Xin , Xue Cong , Shu Ditian , Li Haifeng , Qin Zike , Li Yonghong , Wu Zhiming , Li Zhiyong , Yao Kai , Liu Zhuowei , Zhou Fangjian , Zhang Pian , Chu Junjun , Zhang Yaer , Ma Junxiang , Weng Desheng , Zhang Xing , Xu Ruihua 
Published: June 2024

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Background: The appropriate treatment for mUC remains unmet medical needs. MASCT-I, an adoptive transfer of dendritic cells (DCs) presenting 15 types of tumor-associated antigens (TAAs), showed valuable treatment in solid tumors. We previously reported the efficacy and safety of MASCT-I alone, or plus camrelizumab or chemotherapy in mUC (NCT03034304). The biomarker analysis and long-term follow-up to for this promising approach was unknown. Methods: All enrolled patients were divided into in five groups (G) as previous reported. Patients in G2 receiving maintenance therapy of MASCT-I after first-line platinum based-chemotherapy were allowed to enter enrolled in G3 and receiving MASCT-I plus camrelizumab when disease progressed. We updated the exploratory endpoint of the IFN-γ ELISPOT assay, which was used to measure activation of the cytotoxic T Lymphocyte (CTL) response in eligible patients. Long-term follow-up results for safety, progression-free survival (PFS) and overall survival (OS) were reported. Results: 39 patients were enrolled. By January 31st, 2024, median follow-up time was 31.1 months. No new safety signals were updated. As previously reported, the most common adverse events (AEs) associated with MASCT-I included grade 1 and 2 flushing, pruritus, rash, muscle cramp, fever, and arthralgia. No MASCT-I-related death occurred. Median PFS and OS for all patients were 2.3 months, and 16.9 months, respectively. Patients in G2 presented superior OS of 41.2 months and duration of response (DOR) of 6.4 months. Nine patients treated with MASCT-I and camrelizumab after progression on MASCT-I in G2 presented a 24-month PFS rate of 55.6% and a 48-month DOR rate of 71.8%. Five patients had prolonged PFS for more than 20 months while two of them had PFS of more than 43 months. To identify the potentially beneficial population, IFN-γ ELISPOT data analysis revealed that patients who had positive TAAs ELISPOT response had significant prolonged PFS and OS compared to the non-responders (median PFS: 10.1 months vs 4.8 months, HR=0.30, 95% CI: 0.14-0.61, P<0.005; median OS: not reached vs 13.6 months, HR=0.16, 95% CI: 0.05-0.57, P<0.005). The Cmax value of INF-γ-positive T cells after cell infusion was also higher in patients with better PFS. In addition, we observed a significant increase in INF-γ-positive T cell activities in patients who progressed from G2 and were subsequently treated with a combination of MASCT-I and camrelizumab (Cmax mean (SD): 72 spots per million bulk PBMCs at G2 to 186 spots per million bulk PBMCs after transfer to G3, P=0.002). Conclusions: MASCT-I alone or in combination with immunotherapy or chemotherapy are safe and well tolerated, with inspiring survival benefit. The combination of PD-1 inhibitors may enhance the antitumor activity of MASCT-I. IFN-γ ELISPOT might be able to predict potentially beneficial populations. Clinical trial information: NCT03034304 .