Clinical trialPhase 3Head and neck cancers

Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial

JAMA · 2023289 patients

Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, et al. JAMA. 2023. 330:1961-1970

Study type: Clinical trial
Study name: JUPITER-02
Phase: Phase 3
Design: International multicentre randomised double-blind trial (1:1) in endemic regions (mainland China, Taiwan and Singapore)
Sample size: 289 patients
Source: JAMA · 2023
Trial registration: NCT03581786

In plain words

Nasopharyngeal cancer (cancer at the back of the nose) is a particular type of head and neck cancer that is often linked to the Epstein–Barr virus. In disease that has come back or spread, adding the immunotherapy drug toripalimab to standard chemotherapy (gemcitabine and cisplatin) lengthened the time the disease stayed under control from about 8 months to more than 21 months and lowered the risk of death by about a third.

Key results

21.4 vs 8.2 months

Median progression-free survival (final PFS analysis)

HR 0.52; 95% CI 0.37–0.73

HR 0.63

Overall survival

95% CI 0.45–0.89; two-sided P 0.008; median follow-up 36.0 months

Not reached vs 33.7 months

Median overall survival

Drugs in this study:Cisplatin (Platinol)Gemcitabine (Gemzar)

Dose and schedule cards

Toripalimab + gemcitabine + cisplatin (JUPITER-02)

First line for metastatic or locally advanced recurrent nasopharyngeal cancer (at least 6 months after the end of definitive treatment)Cycle length: Every 21 daysOn the page “Head and neck cancers” · Nasopharyngeal cancer: locoregionally advanced and recurrent or metastatic

First line for metastatic or locally advanced recurrent nasopharyngeal cancer (at least 6 months after the end of definitive treatment)

Drug	Dose	Route	Schedule
Toripalimab	240 mg	IV; first infusion over 60 minutes, subsequent infusions over 30 minutes if tolerated	Day 1, every 3 weeks
Up to 6 cycles
Gemcitabine	1000 mg/m²	IV	Days 1 and 8
Cisplatin	80 mg/m²	IV	Day 1
Maintenance
Toripalimab	240 mg	IV	Every 3 weeks

Cycle length: Every 21 days
Duration: Chemotherapy up to 6 cycles; toripalimab until progression, unacceptable toxicity or up to 24 months

Patients with autoimmune disease (except stable hypothyroidism or type 1 diabetes) or requiring immunosuppression were excluded. Toripalimab monotherapy after progression on platinum: 3 mg/kg every 2 weeks.

On the page “Head and neck cancers” · Nasopharyngeal cancer: locoregionally advanced and recurrent or metastatic

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Toripalimab + gemcitabine–cisplatin

Toripalimab 240 mg IV every 3 weeks (before chemotherapy) with cisplatin 80 mg/m² IV day 1 and gemcitabine 1000 mg/m² IV days 1 and 8, every 3 weeks for up to 6 cycles; then maintenance toripalimab 240 mg every 3 weeks until disease progression, intolerable toxicity or a maximum of 2 years. Continuation after radiological progression was allowed if there was clinical benefit. According to the FDA label, toripalimab dose reduction is not recommended (only interruption or discontinuation) (146 patients).

2Placebo + gemcitabine–cisplatin

Placebo every 3 weeks with the same cisplatin 80 mg/m² day 1 and gemcitabine 1000 mg/m² days 1 and 8, every 3 weeks for up to 6 cycles; then maintenance placebo every 3 weeks until progression, intolerable toxicity or a maximum of 2 years (143 patients).

Source of the regimen details: Abstract of the paper, ClinicalTrials.gov NCT03581786 and the FDA label for Loqtorzi (DailyMed, section 14)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients aged 18 to 75 years with primary metastatic nasopharyngeal carcinoma (stage IVB, AJCC/UICC 8th edition) or recurrent disease not amenable to locoregional or curative treatment, without prior systemic chemotherapy in the recurrent or metastatic setting; for recurrence after curative treatment, at least 6 months since the last radiotherapy or chemotherapy was required; at least one measurable lesion (RECIST 1.1). Autoimmune disease (except stable hypothyroidism or type 1 diabetes), need for systemic immunosuppression and prior anti-PD-1, PD-L1 or CTLA-4 treatment were exclusion criteria. Randomisation was stratified by ECOG (0 versus 1) and stage (recurrent versus metastatic). Median age 46 years, 17% women.

Endpoints

Primary endpoint: progression-free survival assessed by blinded independent central review. Secondary: objective response, overall survival, investigator-assessed progression-free survival, duration of response and safety.

Safety and side effects

The incidence of all adverse events, grade 3 or higher adverse events and fatal adverse events was similar in the two groups. Discontinuation due to adverse events (11.6% versus 4.9%), immune-related adverse events (54.1% versus 21.7%) and grade 3 or higher immune-related adverse events (9.6% versus 1.4%) were more frequent in the toripalimab group.

According to the FDA label: serious adverse events in 43% of the toripalimab group (most common: thrombocytopenia 14%, decreased neutrophil count 10%, pneumonia 10% and anaemia 9%); fatal adverse events 2.1% (epistaxis, intracranial haemorrhage with immune-related thrombocytopenia, and pneumonia); permanent discontinuation of toripalimab 12% and temporary interruption 50%.

Clinical significance and place in guidelines

JUPITER-02 led to the first FDA approval for the treatment of nasopharyngeal carcinoma (toripalimab, October 2023). The NCCN guideline (version 2.2025) lists toripalimab with gemcitabine–cisplatin as a category 1 preferred option for first-line treatment of recurrent or metastatic NPC. Other anti-PD-1 agents (such as camrelizumab and tislelizumab) have also shown similar results in Chinese trials.

Limitations

All patients came from endemic regions of East Asia, and generalisation to non-endemic NPC (which may not be EBV-related) is uncertain; crossover of placebo patients to immunotherapy after progression was allowed.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.