A phase 1 dose escalation trial of ipilimumab and stereotactic body radiotherapy in metastatic melanoma
Mené sur 13 patients atteints d'un mélanome métastatique, cet essai de phase I évalue la faisabilité d'un traitement combinant de manière concomitante ipilimumab et radiothérapie corporelle stéréotaxique avec escalade de doses
Purpose : Ipilimumab can induce durable responses in patients with metastatic melanoma. Unfortunately the majority of patients do not respond to ipilimumab in monotherapy. Preclinical data and early clinical data suggest synergistic antitumor activity between ipilimumab and high-dose radiotherapy. Here, we report the results of our phase I trial, evaluating safety of the ipilimumab/radiotherapy combination. Methods and Materials : Thirteen patients with metastatic melanoma were enrolled. Trial treatment consisted of 4 cycles of ipilimumab in combination with concurrent dose-escalated high-dose radiotherapy to one lesion administered prior to the 3rd cycle of ipilimumab. Results : Grade 3 or 4 ipilimumab-related adverse events occurred in 25% of patients. The maximum tolerated radiotherapy dose was not reached. Local control of the irradiated lesions was achieved in 11 of 12 irradiated patients (one patient had progressive disease prior to irradiation and dropped out of the trial). Evaluation of the non-irradiated lesions demonstrated that 3 of 13 patients experienced clinical benefit, with one patient developing a partial response and two 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 radiotherapy might be more effective if combined with ipilimumab. Conclusion : Our findings suggest that the combination of ipilimumab and high-dose radiotherapy is feasible and safe.