Phase 1 Dose Escalation Trial of Ipilimumab and Stereotactic Body Radiation Therapy in Metastatic Melanoma

Int J Radiat Oncol Biol Phys. 2018 Mar 15;100(4):906-915. doi: 10.1016/j.ijrobp.2017.11.029. Epub 2017 Nov 24.

Abstract

Purpose: To report the results of a phase 1 trial evaluating the safety of the ipilimumab/radiation therapy combination in patients with metastatic melanoma.

Patients and methods: Thirteen patients with metastatic melanoma were enrolled. Trial treatment consisted of 4 cycles of ipilimumab in combination with concurrent dose-escalated high-dose radiation therapy to 1 lesion administered before the third cycle of ipilimumab.

Results: Grade 3 or 4 ipilimumab-related adverse events occurred in 25% of patients. The maximum tolerated radiation therapy dose was not reached. Local control of the irradiated lesions was achieved in 11 of 12 irradiated patients (1 patient had progressive disease before irradiation and dropped out of the trial). Evaluation of the nonirradiated lesions demonstrated that 3 of 13 patients experienced clinical benefit, with 1 patient developing a partial response and 2 patients having confirmed stable disease. Immunomonitoring data showed that in patients without clinical benefit, factors linked to immunotolerance increased early after the initiation of ipilimumab, suggesting that early initiation of radiation therapy might be more effective if combined with ipilimumab.

Conclusions: Our findings suggest that the combination of ipilimumab and high-dose radiation therapy is feasible and safe.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / adverse effects
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Female
  • Humans
  • Immune Tolerance
  • Ipilimumab / administration & dosage*
  • Ipilimumab / adverse effects
  • Male
  • Maximum Tolerated Dose
  • Melanoma / immunology
  • Melanoma / secondary*
  • Melanoma / therapy*
  • Middle Aged
  • Radiosurgery / methods*
  • Radiotherapy Dosage
  • Response Evaluation Criteria in Solid Tumors
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • Ipilimumab