FDA Grants Priority Review to Toripalimab +/- Chemotherapy in Advanced NPC

The FDA has accepted a biologics license application (BLA) for toripalimab both in combination with gemcitabine and cisplatin for the first-line treatment of patients with advanced recurrent or metastatic nasopharyngeal carcinoma (NPC) as well as a monotherapy for the second-line or above treatment of recurrent or metastatic NPC after platinum-containing chemotherapy.¹

According to a press release issued by Junshi Biosciences Co., Ltd, the BLA was granted priority review designation with a Prescription Drug User Fee Act date of April 2022. A meeting of the Oncologic Drugs Advisory Committee is planned to discuss the application.

“We are excited by the continued progress of toripalimab toward a first marketing authorization outside of China,” said Patricia Keegan, MD, chief medical officer of Junshi Biosciences. “With the earlier approval in China, toripalimab became the world’s first immune checkpoint inhibitor for the treatment of nasopharyngeal carcinoma, bringing a novel therapy to a disease that has long lacked new drug development. We will cooperate closely with our partner, Coherus, to leverage the FDA’s priority review designation to accelerate the completion of the BLA review and believe toripalimab, if approved, will bring an important new treatment option for NPC patients in the United States.”

The BLA for toripalimab is supported by findings from the phase 2 POLARIS-02 trial (NCT02915432) and the phase 3 JUPITER-02 trial (NCT03581786).

For use alone in the second-line or above treatment of patients with recurrent or metastatic NPC, results from the POLARIS study showed that toripalimab has a manageable safety profile and can elicit durable clinical responses.²

A total of 190 patients were included in the single-arm, multicenter phase 2 study. Patients received 3 mg/kg toripalimab once every 2 weeks until confirmed disease progression or unacceptable toxicity. Patients were assessed for the primary end point of objective response rate (ORR), as well as the secondary end points of safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results showed an ORR of 20.5% (95% CI, 15.0%-27.0%), and a disease control rate (DCR) of 40.0% (95% CI, 33.0% -47.3%). Further, there was a 38.4% decrease in target lesions from baseline.

In terms of the secondary end points, the median DOR was 12.8 months (95% CI, 9.4 to not estimable), the median PFS was 1.9 months (95% CI, 1.8-3.5), and the median OS was 17.4 months (95% CI, 11.7-22.9).

The most common treatment-related adverse events (TRAEs) observed with toripalimab were hypothyroidism (23.7%), anemia (15.3%), and aspartate aminotransferase increase (15.3%).

As a treatment option in combination with chemotherapy, results from the randomized, placebo-controlled, double-blinded JUPITER-02 study supported the potential FDA approval. The study included 289 patients with advanced NPC in the recurrent or metastatic setting who had not received prior chemotherapy. Patients were randomized 1:1 to receive either toripalimab 240 mg in combination with chemotherapy of gemcitabine 1000 mg/m² or cisplatin 80 mg/m² every 3 weeks or matching placebo in combination with either gemcitabine or cisplatin. The primary end point of the study was PFS and the secondary end points included ORR, DOR, and OS.³

After a median treatment duration of 39 weeks in the toripalimab arm compared with 36 weeks in the placebo arm, the median PFS was 11.7 months versus 8.0 months, respectively (HR, 0.52; 95% CI: 0.36-0.74; two-sided P =.0003). A 1 year, the PFS rate was 49% in the toripalimab plus chemotherapy arm compared with 28% with placebo and chemotherapy. Further, the PFS benefit of toripalimab was also shown across the PD-L1 subgroups.

Results for the secondary end points showed an ORR of 77.4% with the toripalimab combination versus 66.4% with placebo (P =.033). The median DOR with toripalimab was 10.0 months compared with 5.7 months in the placebo arm (HR, 0.50; 95% CI,0.33-0.78).

In terms of safety, grade ≥3 AEs were observed in 89.0% of the experimental arm compared with 89.5% of the control arm, but treatment discontinuation only occurred in 7.5% versus 4.9%, respectively.

_References:

_{1. Junshi Biosciences and Coherus announce FDA acceptance of BLA filing for toripalimab for treatment of nasopharyngeal carcinoma. News release. November 1, 2021. Accessed November 1, 2021. https://bit.ly/3nLwvTr}

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

_{3. Xu RH, Mai HQ, Chen QY, et al. JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). J Clin Oncol. 2021; 39(18). doi: 10.1200/JCO.20}