Credit: Matthieu | stock.adobe.com
Findings from the Phase III DIPPER trial (NCT03427827) published by JAMA show that adjuvant camrelizumab administered after induction-concurrent chemoradiotherapy produced a significant improvement in event-free survival (EFS) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).1,2 Camrelizumab was granted Orphan Drug Designation by the FDA for advanced hepatocellular carcinoma (HCC) in April 2021 and is approved for eight indications in China, but has yet to be approved by the FDA.3
“Camrelizumab, a humanized high-affinity anti–PD-1 immunoglobulin G4-κ monoclonal antibody, has significantly improved median progression-free survival from 6.9 months to 9.7 months when combined with chemotherapy in recurrent or metastatic NPC, while maintaining a manageable safety profile,” the study authors wrote. “Based on this finding, camrelizumab has been approved for use in combination with chemotherapy as a first-line treatment in a Chinese Society of Clinical Oncology guideline. However, its value in locoregionally advanced disease remains unclear. Therefore, we hypothesized that adding PD-1 blockade with camrelizumab in an adjuvant setting would provide survival benefit with manageable toxicities for patients with NPC.”1
Camrelizumab attaches to the PD-1 receptor to block the PD-1/PD-L1 signaling pathway, which has been found effective across an array of solid and hematological cancer types. There are currently 50 ongoing clinical trials evaluating camrelizumab for multiple cancer types, including liver, lung, gastric, and breast cancers. In September 2024, manufacturer Elevar Therapeutics Inc., resubmitted a New Drug Application to the FDA for camrelizumab in combination with rivoceranib for the first-line systemic treatment of unresectable HCC.3
Trial Design
The randomized, open-label, multicenter DIPPER trial enrolled 450 patients (mean age, 45 [SD, 10] years; 24% women) with T4N1M0 or T1-4N2-3M0 NPC who previously received induction-concurrent chemoradiotherapy with gemcitabine and cisplatin. The trial was conducted from August 2018 to November 2021 across 11 centers in China, with a final follow-up date of March 20, 2024.
Patients were randomly assigned in a 1:1 ratio to receive adjuvant camrelizumab administered at a dose of 200 mg intravenously once every three weeks for 12 cycles (n = 226) or to receive standard therapy (n = 224). The trial’s primary endpoint was EFS, with secondary endpoints that included distant metastasis-free survival (MFS), locoregional relapse-free survival (RFS), overall survival (OS), safety, and health-related quality of life.
After a median follow-up of 39 months (IQR, 33-50), patients administered camrelizumab had a three-year EFS rate of 86.9%, compared to 77.3% in the standard therapy cohort (stratified hazard ratio, 0.56; 95% CI, 0.36-0.89; P = .01).
For the key secondary endpoints, three-year distant MFS was 92.4% (95% CI, 88.9%-95.9%) in the camrelizumab cohort compared to 84.5% (95% CI, 79.8%-89.6%) in the standard therapy cohort (stratified hazard ratio, 0.54; 95% CI, 0.30-0.97; P = .04); three-year locoregional RFS was 92.8% (95% CI, 89.3%-96.4%) in the camrelizumab cohort compared with 87.0% (95% CI, 82.5%-91.7%) in the standard therapy cohort (stratified hazard ratio, 0.53; 95% CI, 0.28-0.99; P = .046); and three-year OS was 96.4% in the camrelizumab cohort (95% CI, 93.9%-98.9%) compared to 92.9% (95% CI, 89.5%-96.5%) in the standard therapy cohort (stratified hazard ratio, 0.80; 95% CI, 0.35-1.82; P = .59), which did not achieve statistical significance at the time of the analysis.
In terms of safety, grade 3 or 4 adverse events (AE) were reported by 23 patients (11.2%) in the camrelizumab cohort compared to seven patients (3.2%) in the standard therapy cohort. Investigators did not observe a significant decrease in quality of life among patients in the camrelizumab cohort.
“In the primary analysis of the DIPPER study, adjuvant PD-1 blockade significantly improved event-free survival compared with observation alone. The improvement was evident by a 44% reduction in the risk of disease relapse or death, which translated into a 9.6% absolute enhancement in 3-year event-free survival, aligning with the findings in lung cancer and melanoma,” the study authors wrote. “To the best of our knowledge, the DIPPER trial represents the first phase 3 randomized trial of adjuvant immunotherapy to demonstrate the benefit of adding PD-1 blockade after standard induction-concurrent chemoradiotherapy in locoregionally advanced NPC.”1
References
1. Liang Y, Liu X, Shen L, et al. Adjuvant PD-1 Blockade With Camrelizumab for Nasopharyngeal Carcinoma: The DIPPER Randomized Clinical Trial. JAMA. Published online March 13, 2025. doi:10.1001/jama.2025.1132
2. PD-1 Antibody Versus Best Supportive Care After Chemoradiation in Locoregionally Advanced Nasopharyngeal Carcinoma (DIPPER). ClinicalTrials.gov. Updated April 9, 2024. Updated March 19, 2025. https://www.clinicaltrials.gov/study/NCT03427827
3. Elevar Therapeutics Resubmits New Drug Application to FDA for Combination of Camrelizumab plus Rivoceranib as First-Line Treatment Option for Unresectable Hepatocellular Carcinoma Boosted by CARES-310 Leading Overall Survival Analysis. News release. Elevar Therapeutics. September 23, 2024. Updated March 19, 2025. https://elevartx.com/2024/09/23/elevar-therapeutics-resubmits-new-drug-application/