KEY TAKEAWAYS
- The Phase 3 JUPITER-02 trial investigated the efficacy of adding toripalimab, an anti-PD-1 monoclonal antibody, to GP chemotherapy as a first-line treatment for advanced NPC
- The primary endpoint was PFS as assessed by BIRC.
- The addition of toripalimab to GP chemotherapy resulted in a significantly longer PFS and a favorable trend in overall survival compared to chemotherapy alone.
- The safety profile of the combination treatment was manageable, with a higher incidence of investigator-determined irAEs in the toripalimab arm.
Standard first-line therapy for recurrent or metastatic nasopharyngeal cancer(RM-NPC) is the chemotherapeutic combination gemcitabine-cisplatin (GP). In the interim analysis of the JUPITER-02 study (NCT03581786), a randomized, placebo-controlled, double-blind, international Phase III trial, toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, showed significant improvement in progression-free survival (PFS) as first-line treatment for RM-NPC. The final progression-free survival (PFS) and intermediate overall survival (OS) analyses are presented here.
Patients (n=289) with advanced NPC who had not previously received chemotherapy for relapsed or metastatic disease were randomly assigned (1:1) to receive toripalimab 240 mg (n=146) or placebo (n=143) in combination with gemcitabine and cisplatin every 3 weeks (Q3W) for up to 6 cycles, then monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. The degree of disease (recurrent versus primary metastatic) and the ECOG performance status (ECOG PS 0 vs. 1) at inclusion were used to stratify patients. A blinded independent review committee (BIRC) used RECIST v1.1 to evaluate tumor response. As assessed by BIRC in the study’s primary population of interest, PFS was the primary outcome. Secondary outcomes included investigator-assessed progression-free survival, overall survival, objective response rate(ORR), duration of response(DOR), and safety.
The median follow-up for the toripalimab arm was 22.1 months; the placebo arm was 21.4 months as of the PFS analysis cutoff date of June 8, 2021. According to BIRC, the median PFS in the toripalimab arm was 21.4 months, compared to 8.2 months in the placebo arm (HR=0.52, 95% CI: 0.37-0.73), two-sided p<0.0001. PFS rates at 1 year were 59.0% versus 32.9%. Median DOR was 18.0 months versus 6.0 months (ORR, 78.8%; P=0.022); HR, 0.49 (95% CI: 0.33-0.72). Investigator-assessed progression-free survival (PFS) was also substantially better in the toripalimab arm than the placebo arm (median PFS, 17.3 months vs. 8.1 months, HR=0.43 (95% CI: 0.31-0.58), P<0.0001). In either arm, median overall survival (OS) had not been attained as of June 8, 2021. There was a trend towards the toripalimab arm (HR=0.59; 95% CI: 0.37-0.94), P=0.024.
Both progression-free survival (PFS) and overall survival (OS) improved in the toripalimab arm, and these benefits were seen in all save the lowest PD-L1 expression categories. Interestingly, a favorable response was linked to a dynamic decline in plasma Epstein-Barr Virus DNA copy number from baseline. There was no discovery of a new warning sign. Grade 3 AEs were more common in the toripalimab arm (89.7% vs. 90.2%), as were fatal AEs (2.7% vs. 2.8%), while immune-related AEs were more common in the toripalimab arm (53.4% vs. 21.7%). Grade 3 irAEs were more common in the toripalimab arm (8.9% vs. 1.4%).
When combined with GP chemotherapy, toripalimab improved progression-free survival (PFS) and showed a promising overall survival trend in patients with advanced NPC compared to chemotherapy alone.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.LBA2
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03581786
DOI: 10.1200/JCO.2021.39.15_suppl.LBA2 Journal of Clinical Oncology 39, no. 18_suppl
