Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma

Clin Cancer Res. 2020 May 15;26(10):2327-2336. doi: 10.1158/1078-0432.CCR-19-2427. Epub 2020 Feb 7.


Purpose: Rocapuldencel-T is an autologous immunotherapy prepared from mature monocyte-derived dendritic cells (DC), coelectroporated with amplified tumor RNA plus CD40L RNA. This pivotal phase III trial was initiated to investigate the safety and efficacy of a combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with metastatic renal cell carcinoma (mRCC).

Patients and methods: Patients received either Rocapuldencel-T plus standard of care (SOC) or SOC treatment alone. The primary objective compared overall survival (OS) between groups. Secondary objectives included safety assessments, progression-free survival (PFS), and tumor responses based on RECIST 1.1 criteria. Exploratory analyses included immunologic assessments and correlates with OS.

Results: Between 2013 and 2016, 462 patients were randomized 2:1, 307 to the combination group and 155 to the SOC group. Median OS in the combination group was 27.7 months [95% confidence interval (CI) 23.0-35.9] and 32.4 months (95% CI, 22.5-) in the SOC group HR of 1.10 (95% CI, 0.83-1.40). PFS was 6.0 months and 7.83 months for the combination and SOC groups, respectively [HR = 1.15 (95% CI, 0.92-1.44)]. The ORR was 42.7% (95% CI, 37.1-48.4) for the combination group and 39.4% (95% CI, 31.6-47.5) for the SOC group. Median follow up was 29 months (0.4-47.7 months). On the basis of the lack of clinical efficacy, the ADAPT trial was terminated on February 17, 2017. Immune responses were detected in 70% of patients treated with Rocapuldencel-T, and the magnitude of the immune response positively correlated with OS. In addition, we report the survival-predictive value of measuring 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. No serious adverse events attributed to the study medication have been reported to date.

Conclusions: Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immunotherapy, IL-12 produced by the DC vaccine and higher numbers of T regulatory cells present in the peripheral blood of patients with advanced RCC.

Trial registration: NCT01582672.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / therapy*
  • Combined Modality Therapy
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunotherapy / methods*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Sunitinib / therapeutic use*
  • Survival Rate
  • T-Lymphocytes, Regulatory / immunology


  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Sunitinib

Associated data