Rolling Submission for Toripalimab Started for Nasopharyngeal Carcinoma

The filing of a biologics license application has been initiated with the FDA for toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma.

The filing of a biologics license application (BLA) has been initiated with the FDA for toripalimab for the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma.1

Previously, in September 2020, the anti–PD-1 monoclonal antibody was granted a breakthrough therapy designation for use in this patient population based on preliminary data indicating that it may offer substantial benefit over other available therapies.2

“There has been limited development of treatment approaches for patients with advanced nasopharyngeal carcinoma in the United States,” Patricia Keegan, MD, chief medical officer of Junshi Biosciences, stated in a press release. “We are determined to advance effective treatments in the United States by leveraging the successful experience with toripalimab, a safe and effective treatment for previously treated nasopharyngeal carcinoma that is now approved for marketing in China.”

In a phase 1b/2 POLARIS-02 trial (NCT02915432), the safety and activity of toripalimab was evaluated in patients with recurrent or metastatic nasopharyngeal carcinoma, head and neck cancer, gastric cancer, and esophageal cancer.3

Results showed that among the 190 patients in the nasopharyngeal carcinoma cohort, the objective response rate (ORR) achieved with the agent was 20.5% (95% CI, 15.0%-27.0%) with a median duration of response (DOR) of 12.8 months (95% CI, 9.4–not estimable). Moreover, the median progression-free survival (PFS) was 1.9 months (95% CI, 1.8-3.5), and the median overall survival (OS) was 17.4 months (95% CI, 11.7-22.9).

To be eligible for enrollment, patients had to have histologically or cytologically documented

recurrent or metastatic nasopharyngeal carcinoma that was refractory to previous standard chemotherapy; they had to be 18 years of age or older, have measurable disease, and an ECOG performance status of 0 or 1. Patients also needed to have experienced disease progression within 6 months of receiving adjuvant chemotherapy or chemoradiation.

If they received treatment with a monoclonal antibody within 2 weeks prior to the start of the study drug, previously received immune checkpoint inhibitors, or systemic corticosteroids within 1 week prior to treatment initiation, they were excluded. Notably, patients with central nervous system metastases were not permitted.

Study participants received toripalimab at a dose of 3 mg/kg once every 2 weeks via intravenous infusion until progressive disease, unacceptable toxicity, or voluntary withdrawal of informed consent.

The primary end point of the trial was OOR per independent review committee and in accordance with RECIST v1.1 criteria. Key secondary end points comprised safety, DOR, disease control rate, PFS, and OS. Investigators also evaluated PD-L1 expression, plasma Epstein-Barr virus (EPV) DNA copy number, tumor mutational burden, and other genetic biomarkers.

A total of 190 patients were enrolled to the trial; of these patients, 48.4% had previously received 2 or more lines of systemic chemotherapy. The majority of patients in this cohort, or 95.8%, had nonkeratinizing disease, while 4.2% had keratinizing disease.

Additional results from the trial indicated that the ORR was 23.9% (95% CI, 15.6%-33.9%) in 92 patients who progressed on at least 2 lines of prior systemic chemotherapy. Additionally, in patients with PD-L1 positivity, the ORR was 27.1% vs 19.4% in those who were PD-L1 negative (P = .31); however, the difference was not statistically significant. Moreover, those who had a 50% or more decrease in plasma EBV DNA copy number on day 28 experienced a significantly better ORR vs those with less than a 50% decrease, at 48.3% vs 5.7%, respectively (P = .0001).

Treatment-related adverse effects were experienced by 74.2% (n = 141) of patients, and 14.2% (n = 27) experienced toxicities that were grade 3 or higher in severity. The most frequently experienced toxicities included hypothyroidism (23.7%), hyperthyroidism (2.6%), abnormal liver function (1.6%), interstitial lung disease (1.6%), dermatomyositis (0.5%), and autoimmune myocarditis (0.5%).

“Toripalimab could address a significant unmet medical need as a new treatment for advanced nasopharyngeal carcinoma, and we are encouraged by the initiation of the BLA submission,” Denny Lanfear, CEO of Coherus, added in the release.


1. Junshi Biosciences and Coherus BioSciences announce initiation of rolling submission of BLA for toripalimab to the US FDA for the treatment of nasopharyngeal carcinoma. News release. Shanghai Junshi Biosciences Co, Ltd. March 3, 2021. Accessed March 4, 2021.

2. Junshi Biosciences receives FDA breakthrough therapy designation for toripalimab for the treatment of nasopharyngeal carcinoma. News release. Junshi Biosciences. September 10, 2020. Accessed March 4, 2021.

3. Wang F-H, Wei X-I, Feng J, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: a phase 2 clinical trial (POLARIS-02). J Clin Oncol. 2021;39(7):704-712. doi:10.1200/JCO.20.02712