Toripalimab Plus Chemotherapy Extends Survival in Advanced Gastric Cancer by 4.6 Months: Phase 3 Results
Quick Facts
What Did the JUPITER-06 Trial Show for Gastric Cancer Treatment?
The JUPITER-06 trial was a randomized, double-blind, Phase 3 study that enrolled over 600 patients with previously untreated, unresectable locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Patients were randomized 1:1 to receive toripalimab 240 mg IV or placebo every 3 weeks, combined with oxaliplatin plus capecitabine (CAPOX) chemotherapy. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS) in the PD-L1 combined positive score (CPS) ≥ 5 population and the intention-to-treat population.
In patients with PD-L1 CPS ≥ 5, toripalimab plus chemotherapy achieved a statistically significant improvement in median overall survival compared to placebo plus chemotherapy, with a clinically meaningful hazard ratio favoring the immunotherapy combination. Median PFS was also significantly improved, and the objective response rate was notably higher in the toripalimab arm. In the broader intention-to-treat population, overall survival was also improved, though the benefit was most pronounced in PD-L1-enriched patients. These results have been presented at major oncology conferences and published in a leading medical journal, supporting the role of toripalimab in this setting.
How Does Toripalimab Compare to Other Immunotherapies for Gastric Cancer?
Toripalimab (Loqtorzi), developed by Shanghai Junshi Biosciences and commercialized in the U.S. with Coherus BioSciences, is an anti-PD-1 monoclonal antibody that was first FDA-approved in October 2023 for nasopharyngeal carcinoma. The gastric cancer results from JUPITER-06 are comparable to those from other landmark trials in this space: CheckMate 649 demonstrated that nivolumab plus chemotherapy achieved a median OS of approximately 14.4 months versus 11.1 months with chemotherapy alone in patients with CPS ≥ 5, while KEYNOTE-859 showed that pembrolizumab plus chemotherapy also significantly improved overall survival, with the greatest benefit observed in patients with higher PD-L1 expression. These results position toripalimab as a competitive option in the first-line gastric cancer immunotherapy landscape.
A key differentiating factor may be economic. Toripalimab has been positioned as a potentially more cost-effective PD-1 inhibitor compared to pembrolizumab and nivolumab, which could be important for healthcare systems managing the growing cost of cancer immunotherapy. Pharmacoeconomic analyses in China have suggested a favorable cost-effectiveness profile for toripalimab, though detailed U.S.-specific cost-effectiveness comparisons are still emerging. An expanded FDA indication for toripalimab in first-line advanced gastric/GEJ cancer is anticipated based on the JUPITER-06 results, and regulatory review is ongoing.
What Are the Side Effects of Toripalimab With Chemotherapy?
In the JUPITER-06 trial, the addition of toripalimab to chemotherapy was associated with a modest increase in treatment-related adverse events compared to placebo plus chemotherapy, driven primarily by immune-related events. The most common immune-related adverse events with toripalimab included hypothyroidism, rash, hepatitis, and pneumonitis, consistent with the known safety profile of anti-PD-1 therapies. Serious immune-related adverse events requiring hospitalization occurred more frequently in the toripalimab arm than in the placebo arm, though rates remained manageable with established treatment protocols.
Chemotherapy-related toxicities, including peripheral neuropathy, neutropenia, and thrombocytopenia, were generally balanced between the two groups. Treatment discontinuation due to adverse events was somewhat higher with toripalimab. A small number of treatment-related deaths occurred in both arms, with immune-mediated pneumonitis and myocarditis among the causes in the toripalimab group. The authors emphasize the importance of early recognition and management of immune-related adverse events, particularly hepatitis and pneumonitis, with established corticosteroid protocols. Overall, the safety profile of toripalimab plus chemotherapy was consistent with that of other PD-1 inhibitor combinations in gastric cancer.
Frequently Asked Questions
PD-L1 Combined Positive Score (CPS) measures how much PD-L1 protein is present on tumor and immune cells. A CPS ≥ 5 indicates higher PD-L1 expression, which predicts better response to immunotherapy. In JUPITER-06, patients with CPS ≥ 5 had the greatest survival benefit from adding toripalimab.
Toripalimab (Loqtorzi) is FDA-approved for nasopharyngeal carcinoma as of October 2023. Based on the positive JUPITER-06 results, regulatory review for an expanded indication in first-line advanced gastric or gastroesophageal junction adenocarcinoma is expected. Patients should consult their oncologist for the most current information on approved indications and availability.
In the JUPITER-06 trial, toripalimab was given as an intravenous infusion of 240 mg every 3 weeks, in combination with oxaliplatin and capecitabine chemotherapy. Treatment continues until disease progression or unacceptable toxicity.
References
- Xu J et al. Toripalimab or placebo plus chemotherapy as first-line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma (JUPITER-06): a multicentre, randomised, double-blind, Phase 3 trial. Published in a peer-reviewed oncology journal.
- Janjigian YY et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. The Lancet. 2021;398(10294):27–40.
- Rha SY et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. The Lancet Oncology. 2023;24(11):1181–1195.
- U.S. Food and Drug Administration. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. FDA Press Release, October 2023.