JUPITER-02: Toripalimab plus chemo delays NPC progression

Toripalimab added to chemotherapy in the first-line setting delayed disease progression in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC), according to results from the phase III JUPITER-02 trial presented at ASCO 2021.

“The addition of toripalimab to gemcitabine-cisplatin as a first-line treatment for R/M NPC patients provided superior progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and duration of response (DoR) than gemcitabine-cisplatin alone,” remarked study author Dr Rui-hua Xu from Sun Yat-sen University Cancer Center, Guangzhou, China.

“These results support the use of toripalimab in combination with a gemcitabine-cisplatin regimen as a new standard of care for first-line treatment of R/M NPC,” he said.

Participants in this international, double-blind study were 289 Asian patients aged 18–75 years with R/M NPC and ECOG performance status 0–1 with no prior chemotherapy exposure. They were randomized 1:1 to receive up to six cycles of toripalimab (240 mg Q3W; median age 46 years, 85 percent male) or placebo (median age 51 years, 81 percent male) plus gemcitabine (1,000 mg/m² on days 1 and 8) and cisplatin (80 mg/m² on day 1) chemotherapy. Patients then received toripalimab (240 mg) or placebo maintenance Q3W until disease progression, excessive toxicity, investigator’s decision, or consent withdrawal, with a maximum treatment time of 2 years.

About 75 percent of patients were PD-L1–positive, and almost all patients had non-keratinizing squamous cell carcinoma. Fifty-eight and 61 percent of toripalimab and placebo recipients, respectively, had prior radiation therapy.

PFS, assessed by a blinded independent review committee, was significantly improved with toripalimab vs placebo (median 11.7 vs 8.0 months; hazard ratio [HR], 0.52, 95 percent confidence interval [CI], 0.36–0.74; p=0.0003), with 49.4 and 27.9 percent, respectively, progression-free at 1 year. [ASCO 2021, abstract LBA2]

The results were consistent in multiple subgroups.

OS was immature at time of analysis, though a 40 percent reduction in mortality was noted with toripalimab vs placebo (median OS not estimable in either arm; HR, 0.603, 95 percent CI, 0.364–0.997; p=0.0462), with 1-year OS rates of 91.6 percent vs 87.1 percent and 2-year OS rates of 77.8 percent vs 63.3 percent.

ORR was 77.4 and 66.4 percent in the toripalimab and placebo groups, respectively, with complete response achieved in 19.2 percent vs 11.2 percent, partial response in 58.2 percent vs 55.2 percent, and stable disease in 10.3 percent vs 13.3 percent. Median DoR was 10.0 vs 5.7 months in the toripalimab vs placebo group (HR, 0.50, 95 percent CI, 0.33–0.78; p=0.0014).

Grade ≥3 treatment-emergent adverse event (TEAE) rates were similar between the toripalimab and placebo groups (89.0 percent vs 89.5 percent), as were grade ≥3 study drug-related AEs (80.8 percent vs 83.2 percent). Immune-related AEs occurred more frequently with toripalimab vs placebo (7.5 percent vs 0.7 percent). Any-grade AEs led to discontinuation in 7.5 and 4.9 percent of toripalimab and placebo groups, respectively, with no grade ≥3 AEs leading to treatment discontinuation. Four AEs led to death in each group.

The most common grade ≥3 TEAEs in toripalimab and placebo recipients were leukopenia (61.6 percent vs 58.0 percent), neutropenia (57.5 percent vs 63.6 percent), anaemia (47.3 percent vs 39.9 percent), and thrombocytopenia (32.9 percent vs 28.7 percent).

At present, 91 and 54 patients in the toripalimab and placebo groups, respectively, remain on treatment.

According to Xu, NPC is an endemic malignancy in Southern China and Southeast Asia, with incidence rates of 3.0 per 100,000 people in China compared with 1.2 per 100,000 in the rest of the world.

“NPC is challenging as it is typically diagnosed in an advanced stage when current therapy options are extremely limited. The extended response in patients who received toripalimab [in this study] marks a significant advance for treatment of this disease,” he added.

“Treatment advances for late-stage NPC have lagged behind those of other cancers. Findings from the JUPITER-02 study offer new hope for patients with advanced disease, changing how we care for them,” said ASCO Chief Medical Officer and Executive Vice President Dr Julie Gralow, who was not affiliated with the study.