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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.
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2010
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ImmunologyImmunoeditingPhase Ii StudyImmunotherapeuticsImmunotherapyOncologyGenitourinary CancerMetronomic TherapyTumor ImmunityClear Cell RccRadiation OncologyCell TransplantationCancer ResearchHealth SciencesIntradermal InjectionsImmune SurveillanceCancer TreatmentUrologyCancer ImmunosurveillanceImmune Checkpoint InhibitorMedicineCancer TherapeuticsAdvanced Rcc
4588 Background: AGS-003 is an autologous immunotherapy prepared from matured monocyte-derived dendritic cells co-electroporated with the subject's own amplified tumor and synthetic CD40L RNA. Based on previous trial results with AGS-003 and the emergence of tyrosine kinase inhibitors as the standard of care, AGS-003 was evaluated in combination with sunitinib for treatment of advanced RCC. Methods: AGS-003-006 is an open label phase II trial enrolling subjects with newly diagnosed clear cell RCC. Post-nephrectomy, subjects received sunitinib (4wk on, 2wk off) and then concomitant AGS-003 injections (every 3wk × 5 doses, then every 3mo until progressive disease [PD] or end of study). AGS-003 was dosed as 3 intradermal injections containing 1 × 107 cells (targeted to a single lymph node basin). The 1o endpoint was to evaluate clinical activity as measured by the complete response (CR) rate. 2o endpoints included safety; clinical activity via estimates of progression free survival (PFS), overall survival (OS), stable disease (SD), partial response (PR), and CR rates; and measurement of immune response. Results: 25 subjects were enrolled and 21 dosed (intent to treat [ITT]). 3 subjects discontinued before the first dose of AGS-003 and 8 discontinued during treatment due to PD. Baseline characteristics for ITT subjects included median age=56yr (22-68); ECOG performance status, 0=71%, 1=29%; and MSKCC, intermediate risk=15, poor risk=6. Interim results demonstrated that 62% (13/21 subjects) experienced clinical benefit (2 PR, 11 SD). Preliminary median PFS from registration date for the ITT population=12.5 months (95% confidence interval 7.2, N/A). Conclusions: AGS-003 is well tolerated with no immunotherapy-related SAEs or grade 3/4 AEs reported. Promising interim data indicate that AGS-003 in combination with sunitinib yields a median PFS of 12.5 months in subjects with intermediate or poor risk factors. Updated PFS and OS data will be presented. No significant financial relationships to disclose.