Toripalimab/Chemo Combo Granted Breakthrough Therapy Designation by the FDA for First-Line Recurrent or Metastatic Nasopharyngeal Carcinoma


Toripalimab in combination with chemotherapy yielded an improvement in progression-free survival compared with placebo plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma.

The FDA has granted a breakthrough therapy designation for toripalimab (Tuoyi) in combination with gemcitabine and cisplatin as a first line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), according to a press release from Junshi Biosciences and Coherus.1

The breakthrough therapy designation is based on findings from the phase 3 JUPITER-02 trial (NCT03581786) in which the combination elicited an improvement in progression-free survival (PFS). Patients who received the combination experienced a median PFS of 11.7 months vs 8.0 months in the chemotherapy cohort.2

The biologics lcsense application submission for the combination in the second- and third-line setting is anticipated to be complete later in this quarter.

“We are pleased to have received Breakthrough Therapy designation for our novel PD-1 blocking antibody, toripalimab, for nasopharyngeal carcinoma, which is an aggressive cancer with no immuno-oncology treatment options approved in the United States,” Patricia Keegan, MD, chief medical officer at Junshi Biosciences, said in a press release.

The randomized, quadruple blind study, which was presented at the 2021 American Society of Clinical Oncology Annual Meeting, enrolled 289 participants were randomized, 146 of whom were treated with toripalimab at 240 mg plus gemcitabine (1000 mg/m2) and cisplatin (80 mg/m2) on day 1 every 3 weeks for 6 cycles. This was followed by single agent toripalimab maintenance therapy at 240 mg every 3 weeks (n = 146). A total of 143 patients were randomized to the placebo group and were treated with gemcitabine and cisplatin plus placebo every 3 weeks for 6 cycles with the same dosing at the experimental cohort. Placebo maintenance therapy was administered every 3 weeks 

The primary end point of this trial was PFS with key secondary end points including objective response rate, duration of response, disease control rate, and overall survival (OS).

Additional findings from the study indicated that the median OS was not evaluable in either arm (stratified HR, 0.603; 95% CI, 0.364-0.997; P = .0462). Investigators reported that the 1-year PFS rate in the toripalimab arm was 49.4% (95% CI, 36.4%-61.1%) and 27.9% in the placebo arm (95% CI, 18.0%-38.8%).

Moreover, the 1-year OS rate for the toripalimab regimen was 91.6% (95% CI, 85.6%-95.1%) compared with 87.1% in the placebo cohort (95% CI, 80.4%-91.7%). The 2-year OS rate was 77.8% (95% CI, 68.0%-85.0%) for the toripalimab arm and 63.3% (95% CI, 49.8%-74.1%) for the placebo regimen.

Adverse effect (AE) profiles were similar between both the toripalimab and placebo arms, respectively. This included incidence of grade 3 or higher toxicities (89.0% vs 89.5%), infusion reaction of any grade (4.1% vs 4.2%), and fatal AEs (2.7% vs 2.8%). The most common grade 3 or higher AEs included leukopenia (61.6% vs 58.0%), neutropenia (57.5% vs 63.6%), and anemia (47.3% vs 39.9%).

Of the patients who received toripalimab, 39.7% reported immune-related AEs compared with 18.9% in the placebo arm. Additionally, grade 3 or higher toxicities were reported in 7.5% of toripalimab patients and 0.7% in the placebo arm.3

More patients taking toripalimab discontinued treatment due to AEs (7.5%) compared with 4.9% of patients taking the placebo.

The FDA has previously granted breakthrough therapy designation for toripalimab monotherapy for use in recurrent or metastatic NPC for patients with disease progression or after platinum-containing chemotherapy.


1. Junshi Biosciences and Coherus announce U.S. FDA breakthrough therapy designation granted for toripalimab for 1st line treatment of nasopharyngeal carcinoma. News Release. Junshi Bisciences and Coherus. August 12, 2021. Accessed August 13, 2021.

2. Xu R-H, Mai H-Q, Chen Q-Y, et al. JUPITER-02: the randomized, double-blind phase 3 study of toripalimab or placebo plus cisplatin and gemcitabine as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). J Clin Oncol. 2021;39(suppl 15):LBA2

3. Addition of immunotherapy to standard of care first-line regimen delays disease progression in advanced nasopharyngeal carcinoma. News release. ASCO. June 3, 2021. Accessed August 13, 2021.

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