General Information

Loqtorzi (toripalimab-tpzi) injection is a programmed death receptor-1 (PD-1)- blocking antibody.

Loqtorzi is specifically indicated:

• in combination with cisplatin and gemcitabine, for first-line treatment of adults with metastatic or with recurrent locally advanced nasopharyngeal carcinoma (NPC)
• as a single agent for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy

Dosing/Administration

Loqtorzi is supplied as an injection for intravenous administration.

• in combination with cisplatin and gemcitabine: 240 mg intravenously every three weeks
• as a single agent: 3 mg/kg intravenously every two weeks

First Infusion: Infuse over 60 minutes.

Subsequent Infusions: If no infusion-related reactions occurred during the first infusion, subsequent infusions may be administered over 30 minutes.

Mechanism of Action

Loqtorzi (toripalimab-tpzi) injection is a programmed death receptor-1 (PD-1)- blocking antibody. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Toripalimab-tpzi is a humanized IgG4 monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

Side Effects

Adverse effects associated with the use of Loqtorzi may include, but are not limited to, the following:

in combination with cisplatin and gemcitabine:

• nausea
• vomiting
• decreased appetite
• constipation
• hypothyroidism
• rash
• pyrexia
• diarrhea
• peripheral neuropathy
• cough
• musculoskeletal pain
• upper respiratory infection
• insomnia
• dizziness
• malaise

Single Agent Loqtorzi:

• fatigue
• hypothyroidism
• musculoskeletal pain

Clinical Trial Results

The FDA approval of Loqtorzi  was based on results of the JUPITER-02 Phase 3 study and the POLARIS-02 Phase 2 study.

JUPITER-02

The randomized, double-blind, placebo-controlled, international study enrolled 289 patients with advanced NPC who had received no prior chemotherapy for recurrent/metastatic disease were randomized 1:1 to receive Loqtorzi 240 mg or placebo in combination with gemcitabine 1000 mg/m² (days 1 and 8) and cisplatin 80 mg/m² (day 1) of every three-week treatment cycle, followed by Loqtorzi or placebo monotherapy every 3 weeks until disease progression, intolerable toxicity, or completion of two years of treatment. 

Loqtorzi combined with chemotherapy significantly improved progression-free survival (PFS), reducing the risk of disease progression or death by 48% compared to chemotherapy alone. Loqtorzi also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), with treatment resulting in a 37% reduction in the risk of death versus chemotherapy alone.

POLARIS-02

In this single-arm, multicenter phase II study, 190 patients with recurrent/metastatic NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. 

In the POLARIS-02 clinical study Loqtorzi demonstrated durable antitumor activity in patients with recurrent or metastatic NPC who failed previous chemotherapy, with an objective response rate (ORR) of 20.5%, a disease control rate (DCR) of 40.0%, and a median OS of 17.4 months.