FDA Grants Breakthrough Therapy Designation for Toripalimab for Frontline Nasopharyngeal Carcinoma

The FDA has granted a breakthrough therapy designation to toripalimab for single-agent use in combination with gemcitabine and cisplatin in the frontline treatment of patients with recurrent or metastatic nasopharyngeal carcinoma.

The FDA has granted a breakthrough therapy designation to toripalimab for single-agent use in combination with gemcitabine and cisplatin in the frontline treatment of patients with recurrent or metastatic nasopharyngeal carcinoma.1

The designation was supported by findings from the phase 3 JUPITER-02 trial (NCT03581786), which showed that the addition of toripalimab to gemcitabine/cisplatin resulted in superior progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and duration of response (DOR) compared with gemcitabine/paclitaxel alone.2

The median PFS per blinded independent review committee (BICR) and RECIST v1.1 criteria in the investigative arm was 11.7 months (95% CI, 11.0–not evaluable) vs 8.0 months (95% CI, 7.0-9.5) in the control arm (stratified hazard ratio [HR], 0.52; 95% CI, 0.36-0.74; P = .0003). The 1-year PFS rates in the toripalimab and control arms were 49.4% and 27.9%, respectively.

Although the median OS was not evaluable yet in either arm, the 1- and 2-year OS rates favored toripalimab/chemotherapy vs chemotherapy alone, at 91.6% and 87.1%, respectively, and 77.8% and 63.3%, respectively. The stratified HR for death was 0.603 (95% CI, 0.364-0.997; P = .0462).

The BICR-assessed ORR in the investigative arm was 77.4% (95% CI, 69.8%-83.9%) vs 66.4% (95% CI, 58.1%-74.1%) in the control arm (P = .0335). The median DOR in the toripalimab/chemotherapy and chemotherapy-alone arms were 10.0 months (95% CI, 8.8–not evaluable) and 5.7 months (95% CI, 5.4-6.8), respectively (HR, 0.50; 95% CI, 0.33-0.78; P = .0014).

Junshi Biosciences announced plans to submit a biologic license application to the National Medical Products Administration and regulatory authorities in other countries in the future.

JUPITER-02 enrolled patients with primary metastatic nasopharyngeal carcinoma following curative-intent therapy who are treatment-naïve for recurrent or metastatic disease, are between the ages of 18 years and 75 years and have an ECOG performance status of 0 or 1. All patients had measurable disease per RECIST v1.1 criteria.

Patients were stratified based on disease (recurrent vs primary) and performance status (0 vs 1). Participants were randomized 1:1 to receive either toripalimab at 240 mg (n = 146) or placebo plus gemcitabine/cisplatin (n = 143) every 3 weeks for up to 6 cycles. Those in the investigative arm then went on to receive maintenance toripalimab at the same dose every 3 weeks and those in the control arm received placebo maintenance.

The primary end point of the trial was PFS per BIRC and RECIST v1.1 criteria, and key secondary end points comprised investigator-assessed PFS, ORR, DOR, disease control rate, and OS, as well as PFS and OS rates at 1 and 2 years.

The median age of study participants across the arms was 48.5 years, 83% were Male, all were Asian, 43% had an ECOG performance status of 1, and 59.5% had recurrent disease. Moreover, 46.5% were current or former smokers, 17% were current or former alcohol users, and 98.5% had a non-keratinizing squamous cell carcinoma histology. Additionally, 28% previously underwent surgery, 59.5% had prior radiation, and 75.5% had PD-L1 positivity.

Regarding safety, all patients experienced any-grade treatment-emergent adverse effects (AEs). In the investigative and control arms, 95.2% and 97.2%, respectively, experienced toxicities associated with study drug, 39.7% and 18.9%, respectively, experienced immune-related AEs. Moreover, 7.5% of patients on the toripalimab arm experienced AEs that resulted in discontinuation vs 4.9% of patients on the chemotherapy-alone arm. Four patients on each arm experienced a fatal AE.

Frequently reported toxicities in the investigative and control arms, respectively, included leukopenia (any-grade, 91.1% vs 94.4%; grade ≥3, 61.6% vs 58.0%), anemia (any-grade, 88.4% vs 94.4%; grade ≥3, 47.3% vs 39.9%), neutropenia (any-grade, 85.6% vs 93.0%; grade ≥3, 57.5% vs 63.6%), nausea (any-grade, 69.2% vs 83.2%; grade ≥3, 1.4% vs 2.8%), and vomiting (any-grade, 67.1% vs 65.7%; grade ≥3, 2.1% vs 2.1%), among others.


  1. Junshi Biosciences and Coherus announces US FDA breakthrough therapy designation granted for toripalimab for 1st line treatment of nasopharyngeal carcinoma. News release. Junshi Biosciences. August 12, 2021. Accessed August 12, 2021. https://bit.ly/2VNAG7e
  2. Xu R-H, Mai H-Q, Chen Q-Y, 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(suppl 15):LBA2. doi:10.1200/JCO.2021.39.15_suppl.LBA2