Promising clinical benefit was demonstrated in the trial of rocapuldencel-T plus standard-of-care therapy (SOC) versus SOC therapy alone in patients with newly diagnosed metastatic renal cell carcinoma (mRCC), according to findings from an analysis presented at ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.
In addition, a statistically significant association between overall survival (OS) and an increase in the number of rocapuldencel-T induced memory T cells was reported.
These promising long-term data come from the phase III ADAPT trial, which is ongoing after trial discontinuation was advised. In February, 2017 the ADAPT trial’s Independent Data Monitoring Committee recommended that the study be halted following a planned interim data review that showed 75% of the targeted number of 290 events (deaths) had been reached and the OS hazard ratio in the rocapuldencel-T/SOC treatment arm was greater than the pre-defined futility boundary of 0.98 for the 3rd interim assessment.
The trial’s sponsor discussed the preliminary trial data with the US Food and Drug Administration (FDA) and the decision was made to keep the ADAPT trial open, based upon the safety profile, maturing survival data, and the mechanism of action of rocapuldencel-T, which involves the induction of long-term memory immune responses. Rocapuldencel-T is an individualised immunotherapy formulated with RNA isolated from each patient's tumour to activate autologous dendritic cells with tumour-specific antigens to induce an immune response including tumour-specific memory T-cells targeting each patient's specific tumour antigens.
Robert Figlin of the Division of Hematology Oncology, Cedars-Sinai Medical Center in Los Angeles, USA presented findings from the ADAPT trial of rocapuldencel-T plus SOC versus SOC in patients with newly diagnosed mRCC.
The trial recruited adults with synchronous, clear cell mRCC who were eligible for nephrectomy. The ADAPT is an ongoing phase III trial that is being conducted at 107 sites across North America, Europe, and Israel.
A total of 462 patients were randomised 2:1 to receive either three 0.2 mL intradermal injections of rocapuldencel-T plus SOC or SOC alone.
Treatment with SOC/rocapuldencel-T showed a potential survival benefit in patients with mRCC
At a median follow-up of 20 months, the majority of patients in both treatment groups were still alive.
A review of data from 154 of the first third of patients randomised having the longest duration of follow-up and least censored data (44%), suggest a potential survival benefit for the combination.
The researchers also observed a statistically significant correlation between OS and an increase in the number of rocapuldencel-T induced memory T cells (CD8+/CD28+/CD45RA-) in the 114 patients who had received 7 doses of rocapuldencel-T and had data that had been analysed.
Rocapuldencel-T was well-tolerated and demonstrated a safety profile that was consistent with that shown in an earlier phase II trial.
Conclusions
The ADAPT trial is ongoing to further evaluate the long-term effects of this well-tolerated individualised immunotherapy. The finding of a potential survival benefit is worthy of further assessment.
Helen Gogas, Professor in Medical Oncology at First Department of Medicine, National and Kapodistrian University of Athens, Greece who discussed the study results has agreed that censoring may impact assessment of both median survival and potential tail-of-the curve effect which is supported by phase II results. However, she doubts this will be a positive trial as >50% of subjects are censored in both treatment groups at interim analysis. The IDMC recommended to discontinue the study for futility and to the best of her knowledge when IDMC recommendation is termination for futility no trial has turned to be positive. Trials may be positive or may be negative. This is clinical research. She pointed out that we have to accept it and it is the reason we conduct phase III randomised clinical trials.
Disclosure
The study was supported by Argos Therapeutics.
Reference
1137O – Figlin R, et al. Interim Analysis of the Phase 3 ADAPT Trial Evaluating Rocapuldencel-T (AGS-003), an Individualized Immunotherapy for the Treatment of Newly-Diagnosed Patients with Metastatic Renal Cell Carcinoma (mRCC).