845P Vidutolimod + pembrolizumab as 2L+ treatment in patients with anti–PD-1–refractory melanoma and adrenal insufficiency: Subgroup analyses of a phase Ib study

Abstract

Corticosteroid replacement therapy (CRT) in patients (pts) with adrenal insufficiency (AI) could reduce the efficacy of immunotherapy. Vidutolimod (vidu) is an immunostimulatory virus-like particle containing a CpG-A Toll like receptor 9 (TLR9) agonist. In a phase 1b study in pts with anti–PD-1–refractory melanoma, vidu + pembrolizumab (pembro) showed promising clinical activity with an objective response rate (ORR) of 23.5% (95% CI, 15.5-33.1). This post hoc analysis assessed the safety and clinical activity in the subgroup of pts with AI on CRT. This study (NCT02680184) enrolled adults with etastatic or unresectable cutaneous melanoma with progressive disease or stable disease after ≥12 weeks of anti−PD-1 treatment (tx), measurable disease per RECIST v1.1, ECOG PS 0/1, and ≥1 lesion accessible for intratumoral (IT) injection. This post hoc analysis included all pts who received IT vidu + IV pembro. Pts with AI were to receive CRT (prednisone-equivalent 5-10 mg daily) and prophylactic stress-dose steroids (50-100 mg hydrocortisone or equivalent orally every 8 hours) before and for 24-48 hours after vidu dosing. The primary objective was safety, and the key secondary objective was ORR. 159 pts received vidu + pembro. All pts had prior anti–PD-1 tx, and 74 pts (46.5%) had prior ipilimumab (ipi) tx. 148 pts (93.1%) had progressive disease on last anti–PD-1 tx. 20 pts (12.6%) had a medical history of AI; 19 of these pts (95.0%) had prior ipi tx. 5 additional pts (3.1%; 4 with prior ipi tx) were diagnosed with AI on study. Grade 3/4 tx-emergent adverse events were reported in 11 pts (55.0%) with prior AI and in 3 pts (60.0%) diagnosed with AI on study. No tx-related deaths occurred. The ORR was 28.0% (7/25; 95% CI, 12.1-49.4) in pts with AI. The safety and ORR of vidu + pembro in pts with AI were consistent with the overall study population, suggesting that simultaneous corticosteroids for AI do not reduce the biologic activity of this combination. A phase 2 study to confirm the efficacy of vidu + anti–PD-1 in pts with PD-1 blockade–refractory melanoma is ongoing (NCT04698187).