A phase II study testing the safety and activity of AGS-003 as an immunotherapeutic in subjects with newly diagnosed advanced stage renal cell carcinoma (RCC) in combination with sunitinib.

Novel Agents and Approaches for Advanced Renal Cell Carcinoma

“…A phase I/II study tested AGS-003 alone and a phase II study tested AGS-003 plus sunitinib. 41 Data from the latter study showed that AGS-003/sunitinib was well tolerated with no grade 3 or greater treatment related AEs reported. It was active with PR in 2 of 21 patients and SD in 11.…”

Immune Therapy for Kidney Cancer: A Second Dawn?

“…42 In a preliminary report, the investigators noted that the combination was well tolerated and associated with encouraging clinical outcomes (median progression-free survival, 12.5 months) in a small group patients with RCC. Further, median overall survival was 29.3 months, which appeared potentially superior to what would be expected in this patient population for sunitinib alone.…”

“…[30][31][32][33][34][35] These insights have encouraged investigators to pursue agents that block downregulation of effector T cells (eg, programmed death 1 [PD-1] and CTLA-4), inhibit tumor-induced immunosuppression (eg, transforming growth factor-beta [TGF-β] antibody, programmed death ligand 1 [PD-L1] antibody) and more specifically activate T cells (eg, CD137 antibody, IL-21), and dendritic cells (eg, toll-like receptor agonists, AGS-003) ( Table 2). [36][37][38][39][40][41][42] Several of these approaches have shown encouraging efficacy in early trials both as single agents and in combination with standard therapies.…”

Trial Watch: Therapeutic vaccines in metastatic renal cell carcinoma

“…No additive toxicity was reported other than grade 1 local reactions. 53 Peripheral blood mononuclear cells (PBMCs) showed decreased Treg levels and increased levels of CD28 C memory cytotoxic T-cells (CTLs) that were positively correlated with improved PFS. 59 A phase III trial is ongoing.…”

“…44 Another promising new approach is adoptive cell therapy using engineered T-cell Chimeric Antigen Receptor (CAR). 45 Clinical trial results for therapeutic RCC vaccines We reviewed 6 clinical trials of RCC-specific therapeutic vaccines administered in an adjuvant or a metastatic setting: three completed phase III trials (Reniale, [46][47] Trovax, [48][49][50] and Vitespen 51 ) and three phase II trials (TG4010, 52 AGS003, [53][54] and IMA901 21 ), as well as a meta-analysis of dendritic cell (DC)-based vaccines in mRCC 55 ( Table 1). The publications were retrieved from a Medline search (from january 2004 to november 2014).…”