An Independent Data Monitoring Committee (IDMC) has recommended halting the phase III ADAPT trial exploring rocapuldencel-T (AGS-003) for the frontline treatment of metastatic renal cell carcinoma (mRCC), following a futility analysis. Despite this advice, Argos Therapeutics, the company developing the autologous dendritic cell immunotherapy, plans to keep the trial open to conduct further data reviews, according to a statement from the company.
In the ADAPT trial, which enrolled 462 patients with mRCC, patients were randomized to receive rocapuldencel-T plus standard therapy compared with standard therapy alone, which primarily consisted of sunitinib (Sutent). The primary endpoint of the study was overall survival, with secondary endpoints focused on progression-free survival and adverse events (AEs).
At the analysis, the IDMC concluded that the trial was unlikely to show an improvement in overall survival. Keeping with observations from an earlier phase II study, treatment with rocapuldencel-T was well-tolerated. Following the review, Argos is also examining the data, along with their clinical and scientific advisors. They plan to discuss the findings with the FDA, prior to determining the next steps for the ADAPT trial.
"We are extremely disappointed with these results, which included 75% of the targeted events needed to permit the primary analysis and assessment of overall survival in the study," Jeff Abbey, president and chief executive officer of Argos Therapeutics, said in a statement. "We sincerely appreciate the patients and investigators who have participated in the ADAPT phase III trial, and remain convinced in the ability of precision immunotherapy to improve the lives of patients."
The production of rocapuldencel-T includes upfront leukapheresis to collect dendritic cells followed by transfecting of the cells with tumor-specific amplified RNA and synthetic truncated human CD40 ligand RNA. After this process, the vaccine is reintroduced into the patient as an intradermal injection, wherein it was meant to elicit a cytotoxic T-cell response through the secretion of IL-12.
Prior to the phase III trial, an open-label 21-patient phase II study had explored rocapuldencel-T for unfavorable-risk mRCC. Patients received sunitinib and then rocapuldencel-T for 5 dose every 3 weeks followed by rocapuldencel-T quarterly and continued sunitinib until progressive disease. Each dose of rocapuldencel-T consisted of three 0.2 mL intradermal injections.
The final median overall survival from the trial was 30.2 months (95% CI, 9.4-57.1), with approximately one-third of patients alive after nearly 4 years of follow-up. The median progression-free survival was 11.2 months (95% CI, 6.0-19.4). The overall clinical benefit rate was 62%, including partial responses (n = 9) and stable disease (n = 4).
The most common AEs were diarrhea (61.9%), fatigue (57.1%), and nausea (52.4%). No grade 3/4 AEs were attributed to rocapuldencel-T; a total of 5 patients experienced grade 3/4 events, including 2 patients with fatigue, 2 with weight decrease, and 1 with diarrhea. Most rocapuldencel-T-related AEs were injection site reactions.
Other trials are currently exploring rocapuldencel-T across a variety of cancer types, including non–small cell lung cancer (NCT02662634) and muscle-invasive bladder cancer (NCT02944357). Additionally, a pilot trial being conducted by the NCI and Roswell Park Cancer Institute is exploring rocapuldencel-T for patients with localized kidney cancer (NCT02170389). At this point, it is unclear how or if the findings from the ADAPT trial will impact these other ongoing investigations.