Abstract
Multiple antigen stimulating cellular therapy (MASCT)-I for metastatic urothelial carcinoma (mUC): A multicenter, phase I study (MASCT-I-1001).
Author
person
Yanxia Shi
Sun yat-sen University Cancer Center, Guangzhou, China
info_outline
Yanxia Shi, Meiting Chen, Xin An, Cong Xue, Ditian Shu, Haifeng Li, Riqing Huang, Zike Qin, Yonghong Li, Zhiming Wu, Kai Yao, Zhuowei Liu, Fangjian Zhou, Desheng Weng, Xing Zhang, Ruihua Xu
Full text
Authors
person
Yanxia Shi
Sun yat-sen University Cancer Center, Guangzhou, China
info_outline
Yanxia Shi, Meiting Chen, Xin An, Cong Xue, Ditian Shu, Haifeng Li, Riqing Huang, Zike Qin, Yonghong Li, Zhiming Wu, Kai Yao, Zhuowei Liu, Fangjian Zhou, Desheng Weng, Xing Zhang, Ruihua Xu
Organizations
Sun yat-sen University Cancer Center, Guangzhou, China, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China, Sun Yat-Sen University Cancer Center, Guangzhou, China, Department of Urology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China, Melanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, Guangzhou, China, Department of Medical Melanoma and Sarcoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China
Abstract Disclosures
Research Funding
No funding received
None.
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.
Clinical status
Clinical
1 clinical trial
7 organizations
3 drugs
3 targets
Clinical trial
Multi-center, Phase I Clinical Study to Evaluate the Safety and Tolerability of Multi-antigen Autologous Immune Cell Injection (MASCT-I) in Patients With Advanced Solid Tumor, and to Preliminarily Evaluate the Anti-tumor Efficacy of MASCT-I Alone, in Combination With Chemical Drugs, and in Combination With PD1 AntibodyStatus: Recruiting, Estimated PCD: 2023-07-01
Organization
Melanoma and Sarcoma Medical Oncology Unit, Sun Yat-sen University Cancer Center, Guangzhou, ChinaOrganization
Department of Medical Melanoma and SarcomaDrug
MASCT-IDrug
camrelizumabDrug
AN0025Target
MASCT-I