Toripalimab Immunotherapy Receives FDA Approval for Nasopharyngeal (Upper Throat) Cancer

The First Immunotherapy Approval for Nasopharyngeal Cancer

On 27 October 2023, the Food and Drug Administration (FDA) in the United States approved toripalimab-tpzi (Loqtorz, Coherus BioSciences), an immunotherapy drug, combined with cisplatin and gemcitabine chemotherapy for adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma as first-line treatment.

The FDA also approved treatment after progression on platinum-based chemotherapy: toripalimab-tpzi as a single agent for adults with recurrent unresectable or metastatic nasopharyngeal cancer (second-line treatment).

Toripalimab-tpzi is an anti-PD-1 monoclonal antibody immunotherapy. The indications apply regardless of patients' PD-L1 status.

In a press release, Coherus CEO Denny Lanfear said the company was particularly excited about “now turning our attention to developing Loqtorz across multiple tumor types in combination with [immuno-oncology] agents targeting the tumor microenvironment”, including other agents being developed by the company.

The anatomical region called the nasopharynx is known in Turkish as “geniz,” sometimes also described as the “upper pharynx.” It lies behind the nasal cavity, between the upper oral cavity and the upper pharynx. Nasopharyngeal carcinoma therefore means cancer of this region.

A tumor in the nasopharynx (upper throat) is illustrated below:

JUPITER-02: The Trial Leading to First-Line FDA Approval

Toripalimab-tpzi with cisplatin and gemcitabine was evaluated in JUPITER-02, involving 289 patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma who had not received systemic chemotherapy for recurrent or metastatic disease.

This was a randomized, multicenter, double-blind, placebo-controlled trial. Patients were assigned 1:1 to toripalimab-tpzi with cisplatin and gemcitabine followed by toripalimab-tpzi, or cisplatin and gemcitabine followed by placebo.

The primary efficacy endpoint was progression-free survival (PFS). Overall survival was an additional endpoint.

PFS improved significantly with toripalimab-tpzi-containing versus placebo-containing regimens, with medians of 11.7 months and 8 months, respectively (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.36–0.74, P = 0.0003).

Overall survival also improved significantly. Median overall survival was not estimable with the toripalimab-tpzi regimen (95% CI = 38.7 months to not estimable), versus 33.7 months with placebo (95% CI = 27.0–44.2 months) (HR = 0.63, 95% CI = 0.45–0.89, P = 0.0083).

POLARIS-02: The Trial Leading to Second-Line FDA Approval

Toripalimab-tpzi's effectiveness as a single agent was evaluated in POLARIS-02 in 172 patients with unresectable or metastatic nasopharyngeal carcinoma who had previously received platinum-based chemotherapy or whose disease progressed within 6 months of completing it.

This was an open-label, multicenter, single-country, multicohort trial. Patients received toripalimab-tpzi until disease progression or unacceptable toxicity.

The main efficacy endpoints were overall response rate and response duration.

• The overall response rate was 21% (95% CI = 15%–28%), and median response duration was 14.9 months (95% CI = 10.3 months to not estimable).

Side Effects

Immunotherapy-related side effects occurred with toripalimab-tpzi, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.

The most common (≥ 20%) adverse reactions with toripalimab-tpzi plus cisplatin and gemcitabine were nausea, vomiting, decreased appetite, constipation, hypothyroidism, rash, fever, diarrhea, peripheral neuropathy, cough, musculoskeletal pain, upper respiratory tract infection, insomnia, dizziness, and weakness.

The most common (≥ 20%) adverse reactions with single-agent toripalimab-tpzi were fatigue, hypothyroidism, and musculoskeletal pain.

The recommended toripalimab-tpzi dose with cisplatin and gemcitabine is 240 mg every 3 weeks until progression, unacceptable toxicity, or a maximum of 24 months. For previously treated nasopharyngeal carcinoma, the recommended dose is 3 mg/kg every 2 weeks until progression or unacceptable toxicity.