NCT01810016

NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma

Phase I Study of NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma, for Whom Treatment With Ipilimumab is Indicated

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a Phase 1, open-label, non-randomized study of the combination of NY-ESO-1 plus ipilimumab in patients with unresectable or metastatic melanoma for whom treatment with ipilimumab was indicated. Patients must have had evidence of NY-ESO-1 or LAGE-1 tumor positivity and radiologically measurable disease by the immune-related Response Criteria (irRC). Primary study objectives were to determine the safety and tolerability of the combination and to evaluate humoral and cellular immune response. Secondary objectives were to evaluate tumor response and immunological changes in the tumor microenvironment.

Detailed description

Patients were enrolled sequentially, alternating among 3 treatment arms. Study treatment comprised ipilimumab 3 mg/kg administered intravenously (IV) over 90 minutes every 3 weeks for 4 doses followed by the NY-ESO-1 vaccine administered subcutaneously (SC). Arm A received the NY-ESO-1 recombinant protein mixed with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (Poly-ICLC) and Montanide; Arm B received NY-ESO-1 overlapping long peptides 4 (OLP4) mixed with Poly-ICLC and Montanide; and Arm C received NY-ESO-1 OLP4 mixed with Poly-ICLC (without Montanide). The vaccine was administered immediately following the ipilimumab infusion, and patients were observed for 1 hour following administration. No dose adjustments or delays were permitted. Because the study treatment regimens had not been previously investigated in humans, the first patient in each treatment arm was followed for 28 days and evaluated for any regimen-limiting toxicity (RLT), defined as any dose-limiting toxicity (DLT) that could not be attributed solely to either the vaccine or ipilimumab and was therefore considered to be related to the combination. If an RLT was observed in the first patient, the second patient was to be evaluated for 28 days before the third patient was enrolled. If at any point ≥ 2 RLTs were observed in a treatment arm, accrual to that arm was to be terminated and the combination in that arm was to be declared unsafe. Patients were monitored for safety, immune and tumor response, and immunological changes in the tumor microenvironment for the duration of study participation, which may have been up to 6 months.

Conditions

• Unresectable or Metastatic Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	Ipilimumab	Ipilimumab was administered IV over 90 minutes at a dose of 3 mg/kg directly preceding the NY-ESO-1 injection every 3 weeks for 4 doses.
BIOLOGICAL	NY-ESO-1 Protein Vaccine	NY-ESO-1 recombinant protein (250 µg) was mixed with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
BIOLOGICAL	NY-ESO-1 OLP4 Vaccine with Poly-ICLC and Montanide	NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and Montanide ISA-51 VG (1 mL) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.
BIOLOGICAL	NY-ESO-1 OLP4 Vaccine with Poly-ICLC	NY-ESO-1 OLP4 (1 mg) was mixed in 5% dextrose solution in water with Poly-ICLC (1 mg) and administered SC directly following the ipilimumab infusion every 3 weeks for 4 doses.

Timeline

• Start date: 2014-01-24
• Primary completion: 2016-05-17
• Completion: 2016-05-17
• First posted: 2013-03-13
• Last updated: 2022-10-12
• Results posted: 2018-11-30

Locations

5 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated drug study