Multiple antigen stimulating cellular therapy (MASCT)-I for metastatic urothelial carcinoma (mUC): A multicenter, phase I study (MASCT-I-1001)

e16572 Background: Immune checkpoint inhibitors (ICIs) showed unsatisfactory efficacy in mUC. This study aimed to evaluate the role of MASCT-I alone, or plus camrelizumab or chemotherapy in patients (pts) with mUC. Methods: Eligible pts were enrolled in five groups (G): MASCT-I alone as salvage treatment in pts who failed standard treatment (G1), or as maintenance therapy following first-line platinum based-chemotherapy (G2); MASCT-I plus camrelizumab in pts who had progressed after first-line chemotherapy (G3) or ICI (G4), and MASCT-I plus platinum-based chemotherapy as first-line treatment (G5). Pts in G2 were allowed to be enrolled in G3 when disease progressed. The primary endpoint was safety. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). Dynamic biomarker analysis of specific immune responses against 15 antigens was performed by enzyme-linked immunospot assays (ELISPOT) in peripheral blood mononuclear cells from pts. Results: Thirty-nine pts were included from February 16 th , 2017 to March 3 rd , 2022, with two, 18, nine, four and six pts in G1, 2, 3, 4 and 5, respectively. The pts were 37-72 years old, and 69.2% were male. The main MASCT-I-related adverse events (AEs) included grade 1/2 flushing, pruritus, rash, muscle cramp, fever, and arthralgia. Two pts experienced serious AEs related to both MASCT-I and camrelizumab, including grade 3 rash, adrenocortical insufficiency, and pleural effusion in one pt, and grade 3 elevated transaminases in another. No MASCT-I-related death occurred. No new safety signal related to chemotherapy or camrelizumab was reported. Thirty-six out of 39 pts had at least one response evaluation, with one complete response, six partial response and 13 stable diseases. The median PFS and OS for all pts was 2.3 months and 15.5 months, respectively. The median PFS and OS for pts in G2 was 3.0 months and 39.3 months, respectively. Pts in G2 presented significantly superior OS compared with pts in other groups ( P< 0.001). In nine pts enrolled in G3 after progression in G2, the OS was significantly longer than other nine pts in G3 (median OS: not reached vs 15.4 months, hazard ratio [HR] = 0.14, 95% confidence interval [CI]: 0.03-0.61, P= 0.034). Among 24 pts with available ELISPOT analysis, six were defined as responders, which showed a significant prolonged PFS and OS compared with the non-responders (median PFS: 10.1 vs 4.5 months, HR = 0.33, 95% CI: 0.13-0.81, P< 0.005; median OS: not reached vs 13.5 months, HR = 0.19, 95% CI: 0.05-0.70, P< 0.005). Conclusions: Both MASCT-I alone or combined with immunotherapy or chemotherapy showed manageable safety profiles. Maintenance of MASCT-I after first-line chemotherapy presented inspiring survival benefit. Synergistic effects between MASCT-I and ICIs may exist. Potential candidates for MASCT-I treatment may be identified by ELISPOT analysis. Clinical trial information: NCT03034304 .