1373MO - JUPITER-06: A randomized, double-blind, phase III study of toripalimab versus placebo in combination with first-line chemotherapy for treatment naive advanced or metastatic esophageal squamous cell carcinoma (ESCC)

Background

Platinum-based chemotherapy is the standard first-line treatment for advanced or metastatic ESCC. Toripalimab, a humanized monoclonal antibody against PD-1, showed promising efficacy results as first-line treatment for ESCC in combination with paclitaxel plus cisplatin (TP) in a phase Ib trial. Here, we report the results of JUPITER-06 (NCT03829969), a randomized, double-blind phase III trial of toripalimab in combination with TP for advanced or metastatic ESCC.

Methods

Patients with treatment-naïve, advanced or metastatic ESCC were randomized (1:1) to receive 240 mg toripalimab or placebo in combination with TP Q3W up to 6 cycles, followed by toripalimab or placebo maintenance. Stratification factors were ECOG performance score and prior radiotherapy. The primary endpoints were progression-free survival (PFS) by a blinded independent central review (BICR) per RECIST v1.1 and overall survival (OS).

Results

A total of 514 ESCC patients were randomized; 257 in each arm. At a prespecified interim analysis on March 22, 2021, with median follow-up of 7.4 and 7.3 months in the two arms, there was a significant improvement in OS for toripalimab over placebo (HR=0.58 [95% CI: 0.43-0.78], P=0.00037) with median OS of 17.0 vs. 11.0 months. One-year OS rates were 66.0% vs. 43.7%. A significant improvement in PFS by BICR was also detected for toripalimab over placebo (HR=0.58 [95% CI: 0.46-0.74], P<0.00001). The OS and PFS benefits were observed across key subgroups, including all PD-L1 expression subgroups. The incidence of Grade ≥3 adverse events (AEs) (73.2% vs 70.0%) and fatal AEs (8.2% vs 8.2%) were similar between the two arms; however, AEs leading to discontinuation of toripalimab/placebo (11.7% vs 6.2%); immune-related AEs (irAEs) (37.0% vs. 26.5%) and Grade ≥3 irAEs (6.6% vs. 1.6%) were more frequent in the toripalimab arm.

Conclusions

The addition of toripalimab to standard first-line chemotherapy in patients with ESCC showed superior PFS and OS over chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with TP chemotherapy as a new first-line treatment for advanced or metastatic ESCC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Junshi Biosciences and Coherus Biosciences.

Funding

Shanghai Junshi Biosciences and Coherus Biosciences.

Disclosure

R. Xu: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Merk Serono; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca. All other authors have declared no conflicts of interest.