On October 27, 2023, the U.S. Food and Drug Administration (FDA) approved toripalimab-tpzi (Loqtorz) with cisplatin and gemcitabine for first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC). FDA also approved toripalimab-tpzi as a single agent for adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.
Efficacy of toripalimab-tpzi with cisplatin and gemcitabine was evaluated in JUPITER-02 (NCT03581786), a randomized, multicenter, single-region, double-blind, placebo-controlled trial involving 289 patients with metastatic or recurrent, locally advanced NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients were randomized 1:1 to receive either (a) toripalimab-tpzi with cisplatin and gemcitabine, followed by toripalimab-tpzi, or (b) placebo with cisplatin and gemcitabine, followed by placebo. See the full prescribing information for descriptions of the chemotherapy regimens.
The primary efficacy outcome measure was progression-free survival (PFS), as assessed by a blinded independent review committee according to RECIST v1.1. Overall survival (OS) was an additional endpoint. A statistically significant PFS improvement was observed with a median PFS of 11.7 months versus 8.0 months (HR = 0.52; 95% CI = 0.36, 0.74; p = 0.0003) for the toripalimab-tpzi and placebo regimens, respectively. A statistically significant OS improvement was also observed with a median OS not reached (95% CI = 38.7 months, not estimable) for the toripalimab-tpzi regimen and 33.7 months (95% CI = 27.0, 44.2) for the placebo regimen (HR = 0.63; 95% CI = 0.45, 0.89; p = 0.0083).
Efficacy of toripalimab-tpzi as a single agent was evaluated in POLARIS-02 (NCT02915432), an open-label, multicenter, single-country, multicohort trial involving 172 patients with unresectable or metastatic NPC who had received prior platinum-based chemotherapy or had disease progression within six months of completion of platinum-based chemotherapy administered as neoadjuvant, adjuvant, or definitive chemoradiation treatment for locally advanced disease. Patients received toripalimab-tpzi until they experienced 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 a blinded independent review committee 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-tpzi, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions reported in more than 20% of patients receiving toripalimab-tpzi 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 reported in more than 20% of patients receiving toripalimab-tpzi as a single agent were fatigue, hypothyroidism, and musculoskeletal pain.
The recommended toripalimab-tpzi dose with cisplatin and gemcitabine is 240 mg every three weeks until patients experience disease progression or unacceptable toxicity or for up to 24 months. The recommended toripalimab-tpzi dose as a single agent for previously treated NPC is 3 mg/kg every two weeks until patients experience disease progression or unacceptable toxicity.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. The application was granted priority review, breakthrough designation and orphan drug designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov