FDA Greenlights Toripalimab in Advanced Nasopharyngeal Carcinoma


Toripalimab in combination with gemcitabine and cisplatin, as well as toripalimab monotherapy, has been granted approval by the FDA for patients with recurrent, unresectable, or metastatic nasopharyngeal carcinoma.

The FDA has granted approval to the combination of toripalimab-tpzi (Loqtorzi) with cisplatin and gemcitabine for the first-line treatment of adult patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma, and as a monotherapy for the treatment of adult patients with recurrent, unresectable, or metastatic nasopharyngeal carcinoma with disease progression on or after platinum-containing chemotherapy.1

Findings from the phase 3 JUPITER-02 trial (NCT03581786) and the phase 2 POLARIS-02 trial (NCT02915432) support this regulatory decision. Highlights from JUPITER-02 revealed that the first-line treatment combination of toripalimab with chemotherapy reduced the risk of disease progression or death by 48% vs chemotherapy alone (HR, 0.52; 95% CI, 0.36-0.74; P < .0003) in patients with recurrent or metastatic nasopharyngeal carcinoma.2,3

For progression-free survival (PFS) in JUPITER-02, benefits were observed irrespective of PD-L1 status, with patients treated with the combination (n = 146) achieving a median PFS of 11.7 months (95% CI, 11.0–not evaluable [NE]) vs 8.0 months (95% CI, 7.0-9.5) among those in the control arm (n = 143).

Head and neck cancer: © Richman Photo - stock.adobe.com

Head and neck cancer: © Richman Photo - stock.adobe.com

In POLARIS-02, 172 patients with recurrent or metastatic nasopharyngeal carcinoma whose disease progressed on or after prior chemotherapywere included and had an objective response rate (ORR) of 21% (95% CI, 15%-28%). The disease control rate (DCR) observed in these patients was 40.0%, and the median overall survival (OS) was 17.4 months when toripalimab was given alone.4

Further, the median duration of response (DOR) was 14.9 months (95% CI, 10.3–not evaluable), and at 6 and 12 months, the DOR was 83% and 39%, respectively.

“[Toripalimab's] first approval is a pivotal event for Coherus as an innovative oncology company. As a next-generation PD-1 inhibitor it is the keystone of our immuno-oncology [IO] strategy to extend cancer patient survival as shown with the impressive results in NPC,” said Dennis M. Lanfear, chairman and chief executive officer of Coherus, in a press release.1

In JUPITER-02, a randomized, double-blind, placebo-controlled, international, multicenter phase 3 study, 289 patients with advanced nasopharyngeal carcinoma were enrolled if they had received no prior chemotherapy for recurrent/metastatic disease.2 Patients were randomized 1:1 and treated with 240 mg of toripalimab or placebo once every 3 weeks with 1000 mg/m2 of gemcitabine on days 1 and 8 and 80 mg/m2 cisplatin on day 1 of each 3-week cycle. This was followed by toripalimab or placebo monotherapy once every 3 weeks for up to 2 years or until disease progression or intolerable toxicity, or completion of 2 years of treatment. The primary end point of the study was PFS.

Additional data from the trial showed that patients treated with the combination had a statistically significant and clinically meaningful improvement in overall survival (OS). This translated to a 37% reduction in the risk of death compared with patients treated with chemotherapy alone (HR, 0.63; 95% CI, 0.45-0.89; P = .0083). With toripalimab, the median OS was not reached (95% CI, 38.7-NE) vs 33.7 months (95% CI, 27.0-44.2) with chemotherapy.

Toripalimab plus chemotherapy also led to an overall response rate (ORR) of 77%. This included complete response (CR) and partial response (PR) rates of 19% and 58%, respectively. With the combination of toripalimab and chemotherapy, the median DOR was 10 months vs 5.7 months with chemotherapy alone.

For safety, the most common any-grade adverse events (AEs) observed in at least 20% of patients treated with toripalimab plus chemotherapy included nausea (71%), vomiting (68%), decreased appetite (55%), constipation (39%), hypothyroidism (38%), rash (36%), pyrexia (32%), diarrhea (31%), peripheral neuropathy (30%), cough (26%), musculoskeletal pain (25%), upper respiratory infection (23%), insomnia (23%), dizziness (21%), and malaise (21%).1

In POLARIS-02, an open-label, multicenter, multi-cohort trial, patients with unresectable or metastatic nasopharyngeal carcinoma who received prior treatment with platinum-based chemotherapy for recurrent or metastatic nasopharyngeal carcinoma were enrolled. Patients were required to have disease progression within 6 months of completion of neoadjuvant or adjuvant platinum-based chemotherapy, or have received prior definitive chemoradiation treatment for locally advanced disease.

Once enrolled, patients were treated with toripalimab alone at 3 mg/kg once every 2 weeks until disease progression per RECIST v1.1 criteria or unacceptable toxicity. The primary end points of the study were confirmed ORR and DOR per blinded independent review committee assessment.

Additional findings from this study showed that the most common any-grade AEs that occurred in at least 20% of patients were hypothyroidism (27%), fatigue (22%), and cough (20%).1

“We are particularly excited to now turn our attention to developing [toripalimab] across multiple tumor types in combination with IO agents that target the tumor microenvironment, such as our IL27-targeted antibody, casdozokitug, and our CCR8 inhibitor CHS-114, potentially greatly expanding the number of cancer patients achieving improved survival benefit,” said Lanfear in a press release.1

  1. Coherus and Junshi Biosciences announce FDA approval of Loqtorzi (toripalimab-tpzi) in all lines of treatment for recurrent or metastatic Nasopharyngeal carcinoma (NPC). News release. Coherus BioSciences and Shanghai Junshi Biosciences. October 27, 2023. Accessed October 27, 2023. https://tinyurl.com/yfb2that
  2. Mai H, Chen Q, Chen D, et al. Final progression-free survival analysis of JUPITER-02, a randomized, double-blind, phase 3 study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. Presented at: American Association for Cancer Research 2022 Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT226.
  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(suppl 15):LBA2. doi:10.1200/JCO.2021.39.15_suppl.LBA2
  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

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