FDA Approves Toripalimab for Recurrent or Metastatic Nasopharyngeal Carcinoma

October 27, 2023

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

FDA

The regulatory decisions are supported by data from the phase 3 JUPITER-02 trial (NCT03581786) and the phase 2 POLARIS-02 trial (NCT02915432).

“[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,” Denny Lanfear, chairman and chief executive officer of Coherus, stated in a news release. "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.”

JUPITER-02

In JUPITER-02, first-line treatment with the combination of toripalimab and chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma reduced the risk of disease progression or death by 48% vs chemotherapy alone (HR, 0.52; 95% CI, 0.36-0.74; P < .0003). The improvement in progression-free survival (PFS) was observed irrespective of PD-L1 status. Patients treated in the experimental arm (n = 146) achieved a median PFS of 11.7 months (95% CI, 11.0–not evaluable [NE]) vs 8.0 months (95% CI, 7.0-9.5) in the control arm (n = 143).²

Additionally, the combination elicited a statistically significant and clinically meaningful improvement in overall survival (OS), translating to a 37% reduction in the risk of death vs chemotherapy alone (HR, 0.63; 95% CI, 0.45-0.89; P = .0083). The median OS was not reached (95% CI, 38.7-NE) in the toripalimab arm vs 33.7 months (95% CI, 27.0-44.2) for the chemotherapy alone arm.

The randomized, double-blind, placebo-controlled, international, multicenter phase 3 study enrolled 289 patients with advanced nasopharyngeal carcinoma who had received no prior chemotherapy for recurrent/metastatic disease.²

Patients were randomly assigned 1:1 to receive 240 mg of toripalimab or placebo once every 3 weeks in combination with 1000 mg/m² of gemcitabine on days 1 and 8 and 80 mg/m² on day 1 of each 3-week cycle, 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 two years of treatment.

PFS served as the trial's primary end point.

Additional data showed that toripalimab plus chemotherapy elicited an overall response rate (ORR) of 77% of patients, including complete response (CR) and partial response (PR) rates of 19% and 58%, respectively. The median duration of response was 10 months in the experimental arm vs 5.7 months in the chemotherapy alone arm.

In patients treated with toripalimab plus chemotherapy during JUPITER-02, the most common any-grade adverse effects (AEs) reported in at least 20% of patients 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

POLARIS-02

In the POLARIS-02, patients with recurrent or metastatic nasopharyngeal carcinoma whose disease progressed on or after prior chemotherapy (n = 172) experienced an objective response rate (ORR) of 21% (95% CI, 15%-28%), a disease control rate (DCR) of 40.0%, and a median OS of 17.4 months when treated with toripalimab monotherapy.^1,2

The median duration of response (DOR) was 14.9 months (95% CI, 10.3–not evaluable). The 6- and 12-month DOR rates were 83% and 39%, respectively.

The open-label, multicenter, multi-cohort trial enrolled patients with unresectable or metastatic nasopharyngeal carcinoma who received prior treatment with platinum-based chemotherapy for recurrent or metastatic nasopharyngeal carcinoma; had disease progression within 6 months of completion of neoadjuvant or adjuvant platinum-based chemotherapy; or received prior definitive chemoradiation treatment for locally advanced disease.

Patients were excluded if they had prior treatment with an anti–PD-(L)1 or active autoimmune disease or other medical conditions requiring immunosuppressive therapy.

Patients received toripalimab monotherapy at 3 mg/kg once every 2 weeks until disease progression per RECIST v1.1 criteria or unacceptable toxicity.

Confirmed ORR and DOR per blinded independent review committee assessment served as the trial's primary objectives.

In POLARIS-02, the most common any-grade AEs that occurred in at least 20% of patients consisted of hypothyroidism (27%), fatigue (22%), and cough (20%).¹