Recombinant humanized anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma: Results of an open-label phase II clinical study Polaris-03.

Abstract

5040 Background: Patients with advanced metastatic urothelial carcinoma (UC) who experience disease progression after standard therapy have limited treatment options. Phase I study of toripalimab in subjects with heavily pretreated metastatic UC had demonstrated an acceptable safety profile and promising clinical activity. Here we report the safety and efficacy result of toripalimab in a phase II clinical study (POLARIS-03) in Chinese patients with metastatic urothelial carcinoma. (Clinical trial ID: NCT03113266). Methods: Metastatic UC Patients receive toripalimab 3 mg/kg Q2W until disease progression, unacceptable toxicity or voluntary withdrawal. Clinical response is assessed every 8 weeks. Tumor PD-L1 expression and other biomarkers will be evaluated for correlation with clinical response. Results: From May 2017 to September 2019, 204 patients were screened and the study enrollment was completed with 151 patients enrolled from 15 participating centers. The median age was 62 years and 66% were male. 87% patients had visceral metastasis. By the cut-off date of Jan 6, 2020, 92.1% (139/151) patients experienced treatment related adverse event (TRAE) and grade 3 and above TRAE occurred in 35.8% (54/151) patients. Most common TRAE included anemia, triglycerides increased, proteinuria, fatigue, and hyperglycemia. Treatment discontinuation due to a TRAE occurred in 6 (4.0%) patients, while dose delay due to a TRAE occurred in 23 (15.2%) patients. Three patients with major protocol deviations were excluded from efficacy analysis. Among 148 patients assessed by IRC per RECISTv1.1, 2 CR, 36 PR, and 30 SD were observed for an ORR of 25.7% and a DCR of 45.9%. The median DOR was 15.7 months. The median PFS was 1.9 months, and the median OS was estimated 20.8 months. PD-L1 expression results were obtained from 141 patients. PD-L1+ patients (n=46) had significant better ORR than PD-L1- patients (n=95), 41.3% versus 16.8% ( p<0.01). Conclusions: Toripalimab has demonstrated encouraging clinical activity in chemo-refractory UC patients with a manageable safety profile. Patients will be continuously monitored for safety and overall survival. Clinical trial information: NCT03113266 .

Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial

“…Toripalimab, a humanized immunoglobulin G (IgG) 4K monoclonal antibody specific for human PD-1, was approved as a monotherapy for second-line treatment of metastatic melanoma, third-line treatment of advanced nasopharyngeal carcinoma, and second-line treatment of metastatic urothelial carcinoma by the National Medical Product Administration (NMPA) in China (Sheng et al, 2020;Tang et al, 2020;Wang et al, 2021;Wei et al, 2020). Recently, the FDA has granted Breakthrough Therapy Designation to toripalimab monotherapy for patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma with disease progression on or after platinum-containing chemotherapy (Wang et al, 2021) and to toripalimab in combination with gemcitabine and cisplatin as the first-line treatment for advanced or metastatic non-keratinizing nasopharyngeal carcinoma (Mai et al, 2021).…”

Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01)

“…Toripalimab, a humanized IgG 4K monoclonal antibody specific for human PD-1, [7][8][9][10][11] engaged a differential domain on PD-1 than nivolumab and pembrolizumab by a crystal structure analysis. 12 In a preclinical study, toripalimab promoted stronger antigen-specific interferon-g production than nivolumab.…”

Efficacy and safety of transurethral resection of bladder tumour combined with chemotherapy and immunotherapy in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer: a protocol for a randomized controlled trial

“…We record and track the tobacco use of the patients to know their changes in smoking behavior, the information may help us take appropriate measures to promote smoking cessation. The expression of PD-L1 in BC patients has a close relationship with a better objective response rate when compared with PD-L1 negative patients treated with toripalimab in previous studies [37,38], and we record PD-L1 status to further explore the association. We also record the expression of HER-2 because a novel humanized anti-HER-2 antibody conjugated with monomethyl auristatin E, which is called RC48-ADC, has demonstrated a promising efficacy with a manageable safety profile in HER-2 + locally advanced or metastatic UC who had failed at least one line of systemic chemotherapy [43].…”

“…Most irAEs are mild to moderate in severity [42], and extensive clinical use of PD-1/PD-L1 inhibitors has proved to be generally safe [25][26][27]. Toripalimab is a PD-1 inhibitor widely used in China for the treatment of various cancers [36], with satisfactory anti-tumor effects and was generally well-tolerated [36][37][38]. We will closely monitor the potential side effects for early recognition and prompt intervention, and we expect to achieve a better therapeutic effect using the immunochemotherapy regimen without compromising QoL and increasing toxicity.…”

“…Compared with the methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) regimen, the GC regimen provides a similar survival advantage but a better safety profile and tolerability [35]. Toripalimab is a humanized monoclonal antibody against PD-1 developed by Shanghai Junshi Bioscience Co., Ltd, and it was approved by the China National Medical Product Administration in 2021 for the treatment of UC due to its encouraging clinical activity and manageable safety profile [36][37][38]. After 4 cycles of treatment, all participants will be reexamined with urinary cytology and fluorescence in situ hybridization (FISH, a sensitive and specific test used to diagnose UC in urine) [39] and undergo a second TURBT to assess PaR.…”