Drugs Xagena
The Food and Drug Administration ( FDA ) has approved Loqtorz ( Toripalimab-tpzi; Toripalimab ) with Cisplatin and Gemcitabine for the first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma ( NPC ).
FDA has also approved Toripalimab as a single agent for adults with recurrent unresectable or metastatic nasopharyngeal carcinoma with disease progression on or after a Platinum-containing chemotherapy.
Efficacy of Toripalimab with Cisplatin and Gemcitabine was evaluated in JUPITER-02, a randomized, multicenter, single region, double-blind, placebo-controlled trial in 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 either Toripalimab with Cisplatin and Gemcitabine, followed by Toripalimab, or placebo with Cisplatin and Gemcitabine, followed by placebo.
The primary efficacy outcome measure was progression-free survival ( PFS ), as assessed by a Blinded Independent Review Committee ( BIRC ) according to RECIST v1.1. Overall survival ( OS ) was an additional endpoint.
A statistically significant progression-free survival improvement was observed with a median progression-free survival of 11.7 months versus 8.0 months ( hazard ratio [ HR ] 0.52 [ 95% CI: 0.36, 0.74 ], p-value=0.0003 ) for the Toripalimab and placebo-containing regimens, respectively. A statistically significant overall survival improvement was also observed with median overall survival not-reached ( 95% CI: 38.7 months, not-estimable ) for the Toripalimab-containing regimen and 33.7 months ( 95% CI: 27.0, 44.2 ) for the placebo-containing regimen ( HR 0.63 [ 95% CI: 0.45, 0.89 ], p-value=0.0083 ).
Efficacy of Toripalimab as a single agent was evaluated in POLARIS-02, an open-label, multicenter, single country, multicohort trial in 172 patients with unresectable or metastatic nasopharyngeal carcinoma who had received prior 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 until disease progression per RECIST v1.1 or unacceptable toxicity.
The major efficacy outcome measures were confirmed overall response rate ( ORR ) and duration of response ( DOR ) as assessed by BIRC using RECIST v1.1. ORR was 21% ( 95% CI: 15, 28 ) and median DOR was 14.9 months ( 95% CI: 10.3, not-estimable ).
Immune-mediated adverse reactions occurred with Toripalimab, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.
The most common adverse reactions ( greater than or equal to 20% ) for Toripalimab with Cisplatin and Gemcitabine 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 adverse reactions ( greater than or equal to 20% ) for Toripalimab as a single agent were fatigue, hypothyroidism, and musculoskeletal pain.
The recommended Toripalimab dose with Cisplatin and Gemcitabine is 240 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months.
The recommended Toripalimab dose as a single agent for previously treated nasopharyngeal carcinoma is 3 mg/kg every two weeks until disease progression or unacceptable toxicity. ( Xagena )
Source: FDA, 2023
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