Toripalimab-tpzi Approved for Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma.

The FDA has approved toripalimab-tpzi (Loqtorzi, Coherus BioSciences, Inc.) in combination with cisplatin and gemcitabine for first-line treatment of metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC). Additionally, the FDA approved toripalimab-tpzi as a single agent for treatment of recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy. Toripalimab is a humanized immunoglobulin G (IgG) antibody for programmed cell death protein 1 (PD-1). This is the first FDA approval for toripalimab.  

Why it matters—JUPITER-02 (NCT03581786): “There are currently no FDA-approved immuno-oncology therapies for NPC,” wrote Hai-Qiang Mai, Professor at Sun Yat-Sen University Cancer Center in China, and colleagues, in their published results of the JUPITER-02 trial, on which approval was based. “Toripalimab in combination with gemcitabine-cisplatin chemotherapy had shown significant improvement over chemotherapy alone in progression-free survival as first-line treatment for recurrent or metastatic NPC at the interim progression-free survival analysis of JUPITER-02 (NCT03581786) study.”

Why it matters—POLARIS-02 (NCT02915432): “Patients with recurrent or metastatic NPC have poor prognosis, with median overall survival <20 months,” wrote Feng-Hua Wang, of Sun Yat-sen University Cancer Center in China, and colleagues, in their published results of the POLARIS-02 trial, on which approval was based. “Platinum doublet, like cisplatin plus gemcitabine, is the standard first-line treatment for recurrent or metastatic NPC. However, there is no standard treatment option in second-line settings and beyond.”

What they studied: Efficacy of toripalimab-tpzi with cisplatin and gemcitabine was studied in the phase 3, double-blind, placebo-controlled, multicenter JUPITER-02 trial in which 289 patients with metastatic or recurrent, locally advanced NPC were randomized 1:1 to receive 240 mg of toripalimab-tpzi with cisplatin and gemcitabine, followed by toripalimab-tpzi, or placebo with cisplatin and gemcitabine, followed by placebo. Patients included those who had not received previous systemic chemotherapy for recurrent or metastatic disease.

The primary end point measured was progression-free survival, as assessed by a Blinded Independent Review Committee (BIRC) according to RECIST v1.1. An additional efficacy end point measured was overall survival.

Efficacy of toripalimab-tpzi as a single-agent was studied in the phase 2, open-label, multicenter, multicohort POLARIS-02 trial in which 172 patients with unresectable or metastatic NPC were enrolled. Patients included those 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.

The end points measured were confirmed overall response rate and duration of response as assessed by BIRC using RECIST v1.1.

Patients were treated until disease progression per RECIST v1.1 or unacceptable toxicity.

What they found: For the JUPITER-02 trial, progression-free survival was observed to be statistically significant at a median of 11.7 months in the toripalimab-tpzi arm compared with 8.0 months in the placebo arm. As well, overall survival was observed to have a statistically significant improvement with the median overall survival not reached in the toripalimab-tpzi arm compared with a median of 33.7 months for the placebo arm.

For the POLARIS-02 trial, the confirmed overall response rate was 21% and the median duration of response was 14.9 months.

Adverse events: Immune-mediated adverse events occurred with toripalimab-tpzi, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.

The most common adverse events experienced by ≥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 events experienced by ≥20% of patients receiving toripalimab-tpzi as a single agent were fatigue, hypothyroidism, and musculoskeletal pain.

What to know: The description of chemotherapy regimens are described in the full prescribing information, linked below.

Conclusion—JUPITER-02: The addition of toripalimab to cisplatin and gemcitabine chemotherapy as first-line treatment for recurrent or metastatic NPC provided clinically important and highly significant overall survival advantage over cisplatin and gemcitabine alone with a manageable safety profile,” concluded Dr. Mai and colleagues. “These results support the use of toripalimab with cisplatin and gemcitabine chemotherapy as the new standard-of-care for this population.”

Conclusion—POLARIS-02: “In summary, POLARIS-02, the largest prospective clinical study of anti-PD-1 monotherapy in patients with chemo-refractory recurrent or metastatic NPC, showed a manageable safety profile,” concluded Dr. Wang and colleagues. “The response rate and, more importantly, the duration of response have demonstrated that toripalimab provides substantial benefit to patients with metastatic NPC who are receiving later-line therapy.”

Instructions: The recommended dosage of toripalimab-tpzi with cisplatin and gemcitabine is 240 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended dosage of toripalimab-tpzi as a single agent for previously treated NPC is 3 mg/kg every two weeks until disease progression or unacceptable toxicity.

For More Information

Mai HQ, Chen QY, Chen DP, et al (2023). Final overall survival analysis of JUPITER-02: A phase 3 study of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). J Clin Oncol (ASCO Annual Meeting Abstracts), 41(16_suppl). Abstract 6009. DOI:10.1200/JCO.2023.41.16_suppl.6009

Wang FH, Wei XL, Feng J, et al (2021). Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: a phase ii clinical trial (POLARIS-02). J Clin Oncol, 39(7):704-712. DOI:10.1200/JCO.20.02712

Clinicaltrials.gov (2023). The efficacy and safety study of toripalimab injection combined with chemotherapy for nasopharyngeal cancer. NLM identifier: NCT03581786.

Clinicaltrials.gov (2023). The study to evaluate toripalimab (JS001) in patients with advanced GC, ESCC, NPC, HNSCC. NLM identifier: NCT02915432.

Loqtorzi (toripalimab-tpzi) prescribing information (2023). Coherus BioSciences, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761240s000lbl.pdf

US Food and Drug Administration (2023). FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-toripalimab-tpzi-nasopharyngeal-carcinoma

Image credit: Nephron. Licensed under CC BY-SA 4.0 DEED


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