Purpose: Rocapuldencel-T is prepared from dendritic cells, co-electroporated with tumor and CD40L RNA. This pivotal Phase 3 trial investigated the safety and efficacy of combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with mRCC.
Experimental design: Patients received either Rocapuldencel-T plus SOC or SOC treatment alone. The primary objective compared OS between groups. Secondary objectives included safety, PFS and tumor responses. Exploratory analyses included immunological assessments and correlates with OS.
Results: 462 patients were randomized 2:1, 307 to the combination group and 155 to the SOC group. Median OS in the combination and SOC groups was 27.7 months and 32.4 months respectively. PFS was 6.0 months and 7.8 months for the combination and SOC groups respectively. The ORR was 42.7% for the combination group and 39.4% for the SOC group. Immune responses were detected in 70% of patients treated with Rocapuldencel-T. The magnitude of the immune response correlated with OS. Additionally, we report the survival-predictive value of IL-12 produced by the DC vaccine and the observation that high baseline numbers of T regulatory cells are associated with improved outcomes in DC treated patients but are associated with poor outcomes in patients receiving SOC treatment.
Conclusion: Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immuno-therapy, DC vaccine produced IL-12 and higher numbers of T regulatory cells present in the peripheral blood of mRCC patients.
Copyright ©2020, American Association for Cancer Research.
Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results.J Immunother Cancer. 2015 Apr 21;3:14. doi: 10.1186/s40425-015-0055-3. eCollection 2015. J Immunother Cancer. 2015. PMID: 25901286 Free PMC article.
Retrospective analysis on the efficacy of sunitinib/sorafenib in combination with dendritic cells-cytokine-induced killer in metastasis renal cell carcinoma after radical nephrectomy.J Cancer Res Ther. 2018 Jun;14(Supplement):S427-S432. doi: 10.4103/0973-1482.180609. J Cancer Res Ther. 2018. PMID: 29970701
Sunitinib in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to International Metastatic Renal Cell Carcinoma Database Consortium Risk Group.Clin Genitourin Cancer. 2018 Aug;16(4):298-304. doi: 10.1016/j.clgc.2018.04.005. Epub 2018 May 4. Clin Genitourin Cancer. 2018. PMID: 29853320 Free PMC article. Clinical Trial.
Immunotherapy versus standard of care in metastatic renal cell carcinoma. A systematic review and meta-analysis.Cancer Treat Rev. 2018 Nov;70:112-117. doi: 10.1016/j.ctrv.2018.08.007. Epub 2018 Aug 20. Cancer Treat Rev. 2018. PMID: 30145397 Review.
Chemotherapy alone versus chemotherapy plus radiotherapy for adults with early stage Hodgkin lymphoma.Cochrane Database Syst Rev. 2017 Apr 27;4(4):CD007110. doi: 10.1002/14651858.CD007110.pub3. Cochrane Database Syst Rev. 2017. PMID: 28447341 Free PMC article. Review.