Adding toripalimab to the chemotherapy combination of gemcitabine and cisplatin may lead to better efficacy outcomes in patients with advanced nasopharyngeal carcinoma, compared with chemotherapy alone.
The addition of toripalimab to the chemotherapy combination of gemcitabine and cisplatin demonstrated superior progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) compared with chemotherapy alone as first-line treatment of patients with advanced nasopharyngeal carcinoma (NPC).
Notably, there was a 13.2-month improvement in PFS (HR, 0.52; 95% CI, 0.37-0.73; P < .0001), and an 11.7% improvement in ORR (95% CI, 1.7-21.2; P = .0221) with toripalimab and chemotherapy compared with placebo and chemotherapy. Responses in the toripalimab arm were more durable and both PFS and ORR results were deemed significant. OS rates at year 1 and 2 were both higher with the addition of toripalimab vs without.
JUPITER-02 (NCT03581786) is a randomized, placebo-controlled, multicenter, double-blind phase 3 study in which toripalimab plus gemcitabine and cisplatin is challenging gemcitabine and cisplatin alone as the standard of care (SOC) for patients with recurrent or metastatic NPC.
During an interim PFS analysis of JUPITER-02, adding the humanized Ig4k monoclonal antibody specific for PD-1 to chemotherapy led to a superior PFS compared with chemotherapy alone. Data presented in a poster at the AACR Annual Meeting 2022 showed the prespecified final PFS and interim OS results of JUPITER-02.
Between November 2018 and October 2019, 289 patients were enrolled at 35 study sites. Overall, 146 patients were randomized to the toripalimab/chemotherapy arm and 143 were randomized to the chemotherapy/placebo arm. Patients received toripalimab 240 mg or matching placebo in combination with gemcitabine and cisplatin every 3 weeks (Q3W) for up to 6 cycles. Initial treatment was followed by toripalimab monotherapy or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment.
PFS by blinded independent review committee (BIRC) in the intention-to-treat (ITT) population is the primary end point of the ongoing study. The secondary end points include PFS by investigator assessment, OS, ORR, duration of response (DOR), and safety. Patients were stratified by ECOG performance status of 0 vs 1, and whether they had recurrent or primary metastatic disease.
The data cutoff for the final analysis of PFS was June 8, 2021, and patients were followed for a median of 22.1 months in the toripalimab arm compared with 21.4 months in the control arm.
The median PFS observed with toripalimab was 21.4 months compared with 8.2 months in the placebo arm. At 1 year, the PFS rate in the toripalimab arm was 59.0% vs 32.9% in the placebo arm.
Median OS was not yet reached at the data cutoff date but trended in favor of toripalimab (HR, 0.59; 95% CI, 0.37-0.94; P = .0238). At 1 year, the OS rate in the toripalimab arm was 91.6% (95% CI, 85.6%-95.1%) vs 87.1% (95% CI, 80.4%-91.7%) in the placebo arm. The 2-year OS rate observed with toripalimab was 75.1% (95% CI, 65.5%-82.4%) compared with 63.9% (95% CI, 54.2%-72.1%) with placebo.
The ORR in patients treated with toripalimab was 78.8%% vs 67.1% in the placebo arm. Response to toripalimab and chemotherapy were complete responses (CRs) in 26.7% of patients and partial responses (PRs) in 52.1%. In the placebo/chemotherapy arm, 13.3% of patients has CRs and 53.8% had PRs. The median DOR was 18.0 months (95% CI, 10.5 to not evaluable [NE]) in the toripalimab arm compared with only 6.0 months (95% CI, 5.6-8.3) in the placebo arm (stratified HR, 0.49, 0.33-0.72; P = .0003)
According to subgroup analysis data, the PFS benefit observed with toripalimab carried over to most subgroups. The analysis also showed that dynamic decrease of plasma Epstein-Barr Virus DNA copy number from bassline correlated with favorable response.
No new safety signals were identified in the study as of the data cutoff date. Grade 3 or higher AEs were observed in 89.7% of the toripalimab arm compared with 90.2% of the control arm. AEs were fatal in 2.7% of ththe toripalimab arm vs 2.8% of the placebo arm. Investigator-determined immune-related AEs were seen in 53.4% of the toripalimab arm vs 21.7% of the placebo arm. The immune-related AEs were mainly low grade with 8.9% of the toripalimab arm having experienced grade 3 or higher cases vs 1.4% of the placebo arm.
Based on the efficacy and safety demonstrated in JUPITER-02, investigators consider toripalimab plus gemcitabine and cisplatin to be a new SOC for the frontline treatment of patients with recurrent or metastatic NPC.
Mai H, Chen Q, Chen D, et al. Final progression-free survival analysis of JUPITER-02, a randomized, double-blind, phase 3 study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. Presented at: American Association for Cancer Research 2022 Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT226.