On October 27, 2023, the FDA approved toripalimab-tpzi (Loqtorzi; Coherus BioSciences), a PD-1 monoclonal antibody, in combination with cisplatin and gemcitabine chemotherapy, for the first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma, and as a single agent for adults with recurrent, unresectable, or metastatic nasopharyngeal carcinoma that progressed during or after treatment with a platinum-containing chemotherapy. Toripalimab is a next-generation PD-1 inhibitor that blocks PD-1 ligands 1 and 2. The FDA granted toripalimab priority review and breakthrough therapy and orphan drug designation for these indications.
The FDA approved toripalimab plus cisplatin and gemcitabine chemotherapy based on results of the JUPITER-02 study, a randomized, multicenter, single-region, double-blind, placebo-controlled phase 3 clinical trial that included 289 patients with metastatic or recurrent, locally advanced nasopharyngeal carcinoma who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients were randomized (1:1) to toripalimab plus cisplatin and gemcitabine followed by toripalimab, or to placebo plus cisplatin and gemcitabine followed by placebo.
The primary efficacy measure was progression-free survival (PFS), as assessed by a blinded independent review committee according to RECIST version 1.1. Overall survival (OS) was a secondary end point. The PFS was significantly better in the toripalimab plus chemotherapy group versus the placebo plus chemotherapy group, with a median PFS of 11.7 months versus 8 months, respectively (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.74; P=.0003), leading to a 48% risk reduction for disease progression or death with toripalimab plus chemotherapy versus placebo plus chemotherapy. The OS was also significantly better in the toripalimab-containing arm versus the placebo arm, with a median OS not reached (95% CI, 38.7 months-not estimable) versus 33.7 months (95% CI, 27.0-44.2), respectively (HR, 0.63; 95% CI, 0.45-0.89; P=.0083), which translated to a 37% reduction in the risk for death with toripalimab plus chemotherapy.
“Today’s FDA approval of Loqtorzi is very encouraging for those living with NPC [nasopharyngeal carcinoma] who currently have very limited treatment options and are in need of new therapies to treat this aggressive and life-threatening form of cancer,” said Jong Chul Park, MD, Assistant Professor, Harvard Medical School, and Attending Physician, Center for Head and Neck Cancers, Massachusetts General Hospital Cancer Center, Boston, in a press release. “Loqtorzi is a new treatment option that has demonstrated the ability to significantly improve PFS and OS and should quickly emerge as the new standard of care when used in combination with chemotherapy.”
The efficacy of toripalimab as a single agent was evaluated in the POLARIS-02 study, a phase 1b/2, open-label, multicenter, single-country, multicohort trial that included 172 patients with unresectable or metastatic nasopharyngeal carcinoma who had previously received platinum-based chemotherapy or had disease progression within 6 months of completion of platinum-based chemotherapy administered as neoadjuvant, adjuvant, or definitive chemoradiation treatment for locally advanced disease. Patients received toripalimab as a single agent until disease progression per RECIST version 1.1 or until unacceptable adverse events (AEs).
The major efficacy measures in the POLARIS-02 study were overall response rate (ORR) and duration of response (DOR), as assessed by a blinded independent review committee using RECIST version 1.1. The ORR with toripalimab alone was 21% (95% CI, 15-28), and the median DOR was 14.9 months (95% CI, 10.3 months-not estimable).
The most common (≥20%) adverse reactions with toripalimab plus chemotherapy were nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, pyrexia, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory infection, insomnia, dizziness, and malaise.
The most common (≥20%) adverse reactions for toripalimab as a single agent were fatigue, hypothyroidism, and musculoskeletal pain.
As with other PD-1 inhibitors, immune-mediated adverse reactions were reported with toripalimab, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin events.
The recommended dose of toripalimab, when used in combination with cisplatin and gemcitabine, is 240 mg every 3 weeks until disease progression, unacceptable AEs, or for up to 24 months. The recommended dose of toripalimab as a single agent is 3 mg/kg every 2 weeks until disease progression or until unacceptable AEs.
