Phase 1 Study of NY-ESO-1 Vaccine + Ipilimumab (IPI) in Patients with Unresectable or Metastatic Melanoma.

e15175 Background: IPI is an approved immunotherapy for advanced melanoma; it has enhanced spontaneous immunity to NY-ESO-1, a cancer-testis antigen expressed by some melanomas. NY-ESO-1 vaccines have been immunogenic when administered with Montanide ISA-51 (MON) and/or Poly-ICLC (pICLC) adjuvants. This trial assessed IPI combined with NY-ESO-1 vaccines (protein or overlapping long peptides [OLP4]). Primary objectives were to assess safety/tolerability and T-cell responses to NY-ESO-1. Secondary objectives included evaluation of tumor response (irRC). Methods: This Phase 1, open-label study (NCT01810016) enrolled patients (pts) with advanced measurable NY-ESO-1-positive melanoma among 3 arms: IPI (IV 3 mg/kg) + NY-ESO-1 protein + pICLC + MON (Arm A); IPI + NY-ESO-1 OLP4 + pICLC + MON (Arm B); and IPI + NY-ESO-1 OLP4 + pICLC (Arm C) every 3 weeks x 4. Circulating T cell responses were assessed by ex vivo IFN-gamma ELIspot assay. Response was defined as a 2-fold increase with vaccination and an increase of ≥10 IFN-gamma-secreting cells per 105 PBMC. Results: Target enrollment was 27. Eight pts (mean age 64, 6M/2F) were enrolled and treated in Arms A (5), B (2) and C (1). The study closed early due to slow enrollment. Seven pts received all 4 doses of IPI + vaccine. All 8 pts had ≥1 treatment emergent adverse event (TEAE); most common were fatigue, injection site reaction, pruritus, diarrhea, rash, skin induration and pyrexia. Three pts had serious TEAEs (SAEs) and Gr3 TEAEs; 1 pt (Arm C) had Gr4 lactic acidosis. Two pts (Arm A) had Gr3 TEAEs related to IPI: diarrhea (SAE), colitis (SAE) and large intestine hemorrhage (n = 1); and hypophysitis (SAE), nausea, vomiting, fatigue, decreased sodium, dehydration and hypotension (n = 1). Best responses were irSD (n = 4) and irPD (n = 4); 3 of these pts discontinued early due to disease progression (1 died). T-cell responses to NY-ESO-1 were detected in 6 of 8 pts (75%), including 4/5 Arm A, 2/2 Arm B, 0/1 Arm C. Conclusions: IPI + NY-ESO-1 vaccines were well tolerated by most pts, and many related TEAEs were attributable to IPI alone. Circulating T cell responses were induced in most pts and were evident ex vivo, suggesting that IPI may have enhanced T cell responses to NY-ESO-1 protein and OLP4. Clinical trial information: NCT01810016.