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 sunitinibin 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.

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