FDA Accepts BLA Resubmission for Toripalimab in Advanced Nasopharyngeal Carcinoma


The FDA has accepted for review a biologics license application resubmission for toripalimab both in combination and as monotherapy for patients with advanced recurrent or metastatic nasopharyngeal carcinoma, according to an announcement from drug developer Coherus.

The FDA has accepted for review a biologics license application (BLA) resubmission for toripalimab both in combination and as monotherapy for patients with advanced recurrent or metastatic nasopharyngeal carcinoma, according to an announcement from drug developer Coherus.1

The company seeks approval to use toripalimab plus gemcitabine and cisplatin for frontline treatment and as monotherapy for second- or later-line therapy following platinum-based chemotherapy.

In November 2021, the FDA accepted a BLA seeking approval for use of the anti–PD-1 monoclonal antibody as a single agent and in combination with chemotherapy in this population.2 However, in May 2022, the agency issued a complete response letter to that BLA requesting a quality process change.3

The initial and resubmitted BLAs are based on findings from the phase 2 POLARIS-02 trial (NCT02915432) and the phase 3 JUPITER-02 trial (NCT03581786).

In the phase 2 trial, toripalimab elicited an objective response rate (ORR) of 20.5% (95% CI, 15.0%-27.0%) per independent review committee (IRC) assessment in previously treated patients with recurrent or metastatic nasopharyngeal carcinoma (n = 190).4

In the phase 3 trial, the combination of toripalimab and gemcitabine and cisplatin demonstrated a median progression-free survival (PFS) of 11.7 months (95% CI, 11.0–not evaluable) per blinded IRC assessment and by RECIST v1.1 criteria vs 8.0 months (95% CI, 7.0-9.5) with chemotherapy alone (stratified HR, 0.52; 95% CI, 0.36-0.74; P = .0003).5

The FDA has scheduled a new Prescription Drug User Fee Act action date for December 23, 2022. The agency previously stated that the review timeline for the BLA resubmission would be 6 months, allowing for the required onsite inspections in China that have been delayed by travel restrictions tied to the COVID-19 pandemic.

If approved, Coherus plans to launch toripalimab in the United States in the first quarter of 2023.

“Toripalimab would address a critical unmet medical need for patients with nasopharyngeal carcinoma, an aggressive cancer for which there are currently no FDA-approved immunotherapy treatments. We collaborated closely with our partner, Junshi Biosciences, to complete the quality process changes requested by the FDA and facilitate the rapid resubmission of the toripalimab BLA,” Theresa LaVallee, PhD, chief development officer of Coherus, said in a press release.

Toripalimab is an anti–PD-1 monoclonal antibody designed to inhibit PD-1 interactions with its ligands, PD-L1 and PD-L2. The drug also enhances receptor internalization, thereby promoting the immune system’s ability to attack and kill tumor cells.

The POLARIS-02 trial enrolled patients with relapsed metastatic nasopharyngeal cancer, head and neck cancer, gastric cancer, and esophageal cancer who were refractory to prior standard chemotherapy or who had progressed within 6 months of adjuvant chemotherapy or chemoradiation. Eligible patients were at least 18 years of age, had measurable disease, an ECOG performance status of 0 or 1, and adequate organ function.

Investigators administered 3 mg/kg toripalimab every 2 weeks until disease progression, intolerable toxicity, or withdrawn consent.

The primary end point was IRC-assessed ORR by RECIST v1.1 criteria. Secondary end points included safety, duration of response, disease control rate (DCR), PFS, and overall survival (OS).

Additional findings from the phase 2 trial revealed a DCR rate of 40.0% (95% CI, 33.0%-47.3%), a median time to response of 1.8 months (95% CI, 1.8-2.1), and a median DOR of 12.8 months (95% CI, 9.4–not estimable [NE]). 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).

As second-line or later treatment (n = 92), toripalimab induced an ORR of 23.9% (95% CI, 15.6%-33.9%) and a DCR of 41.3% (95% CI, 31.1%-52.1%) per IRC assessment and RECIST v1.1 criteria. In this population, the median DOR was 21.5 months (95% CI, 7.7-NE), the median PFS was 2.0 months (95% CI, 1.8-3.6), and the median OS was 15.1 months (95% CI, 10.4-20.4).

The most common adverse effects (AEs) were hypothyroidism (23.7%), anemia (15.3%), aspartate aminotransferase increase (15.3%), alanine aminotransferase increase (13.7%), asthenia (13.2%), proteinuria (12.6%), leukopenia (10.0%), pyrexia (8.4%), pruritus (8.4%), rash (6.3%), and neutropenia (5.3%). Approximately 14% of patients experienced grade 3 or higher AEs.

JUPITER-02 enrolled patients with primary metastatic nasopharyngeal carcinoma or recurrent disease following curative-intent therapy. Eligible patients needed to be aged 18 and 75 years, have an ECOG performance status of 0 or 1, and have measurable disease per RECIST v1.1 criteria.

Patients were randomized 1:1 to 240 mg toripalimab in combination with gemcitabine plus cisplatin every 3 weeks for up to 6 treatment cycles (n = 146) or gemcitabine/cisplatin alone at the same schedule (n = 143).

Those in the toripalimab arm (n = 115) received the agent as maintenance at 240 mg every 3 weeks. Those in the chemotherapy-alone arm (n = 118) received maintenance treatment with placebo.

The primary end point was PFS per blinded IRC by RECIST v1.1 criteria, with secondary end points of investigator-assessed PFS, ORR, DOR, DCR, and OS.

Data presented during the 2021 ASCO Annual Meeting indicated that the median OS had not yet been reached in either arm (stratified HR, 0.603; 95% CI, 0.364-0.997; = .0462). Additionally, the combination of toripalimab and chemotherapy led to an ORR of 77.4% (95% CI, 69.8%-83.9%) vs 66.4% (95% CI, 58.1%-74.1%) with chemotherapy alone (= .0335). The median DOR with the combination was 10.0 months (95% CI, 8.8-NE) vs 5.7 months (95% CI, 5.4-6.8) with chemotherapy alone (HR, 0.50; 95% CI, 0.33-0.78; = .0014).

The most common AEs that occurred with the combination included leukopenia (91.1%), anemia (88.4%), neutropenia (85.6%), nausea (69.2%), vomiting (67.1%), thrombocytopenia (63.0%), decreased appetite (53.4%), and constipation (39.0%).

“Although the COVID-19 pandemic has created tremendous challenges for everyone, our dedication to bring better treatment options to patients around the world remains steadfast,” added Junshi Biosciences chief medical officer Patricia Keegan, MD. “Through our concerted efforts with our partner, Coherus, we have made continual progress towards obtaining toripalimab’s first marketing authorization outside of China. Over the next several months, we will work closely with the FDA to facilitate the review of this novel drug.”


  1. Coherus and Junshi Biosciences Announce FDA Acceptance of Resubmission of BLA for Toripalimab for the Treatment of Nasopharyngeal Carcinoma. News release. Coherus Biosciences. July 6, 2022. Accessed July 6, 2022. https://bit.ly/3nKM2Dm
  2. Coherus and Junshi Biosciences announce FDA acceptance of BLA filing for toripalimab for treatment of nasopharyngeal carcinoma. News release. Coherus BioSciences, Inc. and Shanghai Junshi Biosciences Co., Ltd. November 1, 2021. Accessed July 6, 2022. https://bit.ly/3CwoLeh
  3. Coherus and Junshi Biosciences receive complete response letter from US FDA for toripalimab BLA. News release. Coherus BioSciences Inc. May 2, 2022. Accessed July 6, 2022. https://bit.ly/3LKpXQ0
  4. 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
  5. 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(suppl 15):LBA2. doi:10.1200/JCO.2021.39.15_suppl.LBA2
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