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AGS-003 plus sunitinib shows promise for advanced renal cell carcinoma
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The combination of AGS-003 and sunitinib yielded supportive immunologic responses and extended survival in intermediate- or poor-risk patients with metastatic renal cell carcinoma, according to data from a phase 2 trial.
AGS-003 (Argos Therapeutics) is a novel autologous immunotherapeutic agent created from the patient’s own dendritic cells co-electroporated with amplified tumor RNA and synthetic CD40L RNA, according to study background.
Asim Amin, MD, PhD, a medical oncologist at the Levine Cancer Institute in Charlotte, North Carolina, and colleagues conducted the phase 2 trial to determine the efficacy and safety of the combination of AGS-003 and sunitinib in patients who were newly diagnosed with intermediate- or poor-risk metastatic renal cell carcinoma (mRCC) following nephrectomy.
The primary endpoint was complete response rate. Secondary endpoints were safety, PFS, OS and clinical benefit.
The analysis included 21 patients who were treated continuously with sunitinib (4 weeks on each 6-week cycle). After the first cycle, patients received AGS-003 every 3 weeks for five doses and then every 12 weeks until disease progression or the study concluded.
Sixty-two percent of patients experienced clinical benefit, including nine patients who achieved partial response and four patients who achieved stable disease. However, there were no complete responses and enrollment terminated early.
The median PFS was 11.2 months (95% CI, 6-19.4) and the median OS was 30.2 months (95% CI, 9.4-57.1) from the time of registration for all patients.
Seven patients (33%) survived for a minimum of 4.5 years and five patients (24%) survived more than 5 years. Two patients remained progression-free with durable responses at the time the study concluded.
AGS-003 was associated with mild injection site reactions, but the most common adverse events were related to the toxicity profile of sunitinib.
“In comparison to the benchmarks established for similar risk mRCC patients treated with targeted therapy, the outcomes in this study were encouraging,” Amin said in a press release. “Mature data from this phase 2 study suggest the combination of AGS-003 plus sunitinib was safe, well tolerated and associated with doubling of the expected median survival and encouraging long-term and 5-year survival.”
The researchers also noted the degree of an increase in CD8-positive, CD28-positive and CD45RA-negative effector/memory T cells after five doses of AGS-003 was associated with improved OS.
Robert Figlin
“AGS-003 is designed to generate a patient and tumor-specific immune response,” study researcher Robert Figlin, MD, FACP, the Steven Spielberg Family chair in hematology oncology and professor of medicine and biomedical sciences at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Center, Los Angeles, said in the release. “Observations from this study indicate than an increase in memory T cells after five doses of AGS-003 was associated with prolonged survival. These important findings are being further evaluated in the ongoing phase 3 ADAPT study.” – by Anthony SanFilippo
Disclosure: The study was funded by Argos Therapeutics. Amin reports no relevant financial disclosures. Figlin reports research funding from and consultant/advisory roles with Argos, Bristol-Myers Squibb, Galena, GlaxoSmithKline, Immatics, Novartis, Onyx and Pfizer. Please see the study for a full list of all other researchers’ relevant financial disclosures.
Perspective
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Guillermo de Velasco, MD
Since the approval of high dose interleukin-2 in 1992, immunotherapy represents the oldest and most promising approach for metastatic renal cell carcinoma (mRCC). After a peak in the early 2000s, interest in immunotherapy declined for several years. However, there has been renewed interest in studying the key role that immunotherapy plays in mRCC (Figure 1). This has resulted in the launch of several clinical trials testing immune-modulating drugs and vaccines. Among these strategies, dendritic cell-based immunotherapy appears to be an option in obtaining a highly specific immune response.
Nevertheless, the specific immune profile/biomarker that drives clinical outcomes has yet to be elucidated. To date, all potential biomarkers for immunotherapy have failed to achieve adequate performance. A comprehensive understanding of immune modulation should help to reveal predictive biomarkers enabling improved patient selection and personalized treatment.
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