The rolling submission of a biologics license application to support the approval of both toripalimab plus gemcitabine- and cisplatin-based chemotherapy as a first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma, as well as toripalimab monotherapy for the second-line or beyond treatment of patients with recurrent or metastatic nasopharyngeal carcinoma after platinum-based chemotherapy has been completed.
The rolling submission of a biologics license application (BLA) to support the approval of both toripalimab plus gemcitabine- and cisplatin-based chemotherapy as a first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma, as well as toripalimab monotherapy for the second-line or beyond treatment of patients with recurrent or metastatic nasopharyngeal carcinoma after platinum-based chemotherapy has been completed, according to an announcement from Junshi Biosciences.1
The application is based on data from the phase 3 JUPITER-02 trial (NCT03581786) which showed that the addition of toripalimab to gemcitabine- and cisplatin-based chemotherapy yielded improved outcomes vs the doublet chemotherapy alone as a first-line treatment for patients with metastatic nasopharyngeal carcinoma, as well as the phase 2 POLARIS-02 trial (NCT02915432), in which toripalimab monotherapy demonstrated a manageable safety profile and durable clinical responses as a second-line treatment for this patient population.2,3
“Toripalimab showed remarkable efficacy in the treatment of advanced nasopharyngeal carcinoma according to the results from [the] POLARIS-02 and JUPITER-02 studies, as recognized by inclusion in plenary and other presentations at leading international medical professional conferences and publications in highly respected scientific journals,” Patricia Keegan, MD, chief medical officer of Junshi Biosciences, said in a press release. “We look forward to working closely with the FDA in the review of this BLA and with our U.S. partner, Coherus, to bring this new treatment option forward as expeditiously as possible for patients in the U.S.”
Results from the JUPITER-02 trial showed that the median progression-free survival (PFS) per RECIST v1.1 criteria by blinded independent review committee (BICR) for toripalimab plus chemotherapy was 11.7 months (95% CI, 11.0-not evaluable [NE]) vs 8.0 months (95% CI, 7.0-9.5) for chemotherapy alone (stratified hazard ratio [HR], 0.52; 95% CI, 0.36-0.74; P = .0003). Additionally, the 1-year PFS rates in the combination and control arms were 49.4% (95% CI, 36.4%-61.1%) and 27.9% (95% CI, 18.0%-38.8%), respectively.
The 1- and 2-year overall survival (OS) rates were also superior with the combination vs chemotherapy alone, at 91.6% and 87.1%, respectively, and 77.8% and 63.3%, respectively. The median OS was not met in either study arm.
Moreover, the objective response rate (ORR) per BICR in the combination arm was 77.4% (95% CI, 69.8%-83.9%) vs 66.4% (95% CI, 58.1%-74.1%) in the chemotherapy alone arm (P = .0335). The median duration of response (DOR) was 10.0 months (95% CI, 8.8-NE) vs 5.7 months (95% CI, 5.4-6.8), respectively (HR, 0.50; 95% CI, 0.33-0.78; P = .0014).
The study enrolled patients with primary metastatic or recurrent nasopharyngeal carcinoma following curative-intent therapy. Patients were treatment naïve for recurrent or metastatic disease, between the ages of 18 years and 75 years, had an ECOG performance status of 0 or 1, and measurable disease per RECIST v1.1 criteria.
The primary end point of the trial was PFS per RECIST v1.1 criteria by BIRC, and key secondary end points were investigator-assessed PFS, ORR, DOR, disease control rate (DCR), and OS, as well as PFS and OS rates at 1 and 2 years.
In August 2021, the FDA 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 regulatory designation was based on the results of the JUPITER-02 trial.
The POLARIS-02 trial examined toripalimab as a treatment for patients with recurrent or metastatic nasopharyngeal carcinoma, head and neck cancer, gastric cancer, and esophageal cancer. Results from the nasopharyngeal carcinoma cohort showed that among 190 evaluable patients, the ORR was 20.5% (95% CI, 15.0%-27.0%) with the agent, and the median DOR was 12.8 months (95% CI, 9.4-NE). Additionally, 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 primary end point of the trial was ORR, and key secondary end points were safety, DOR, DCR, PFS, and OS.
In September 2020, the FDA granted a breakthrough therapy designation to toripalimab monotherapy for patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma with disease progression on or after platinum-containing chemotherapy.
“Toripalimab, the foundation stone of our emerging immuno-oncology franchise, demonstrated compelling efficacy in the pivotal studies supporting the BLA for nasopharyngeal carcinoma,” Denny Lanfear, chief executive officer of Coherus, said in a press release. “As data read out from the extensive set of pivotal clinical trials potentially supporting a broad range of additional indications, we expect toripalimab to maintain a consistently strong efficacy profile. We will continue to work with our partner, Junshi Biosciences, to advance toripalimab through FDA approval.”