Phase II trial of ipilimumab monotherapy in melanoma patients with brain metastases.
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.8523
ISSN1527-7755
AutoresDonald P. Lawrence, Omid Hamid, David F. McDermott, Igor Puzanov, Mario Sznol, Jordan J. Clark, T. Logan, F. Stephen Hodi, Kevin N. Heller, Kim Margolin,
Tópico(s)CAR-T cell therapy research
Resumo8523 Background: Ipilimumab (Ipi), a human monoclonal antibody that blocks CTLA-4, has activity in advanced melanoma. We present results from a phase II trial (CA184-042) to assess Ipi safety and activity in advanced melanoma patients (pts) with brain metastases (mets). Methods: This 2-stage trial required > 2 objective responses (ORs) among the first 21 pts in order to proceed to stage 2 of Arm A and to open Arm B. Ptshad measurable brain mets with at least one lesion > 0.5 cm and/or 2 lesions > 0.3 cm, and none > 3 cm in diameter. Prior whole brain radiotherapy and stereotactic radiotherapy to non-index lesions were allowed. Pts were steroid-free (Arm A) or required steroids for symptoms of brain mets at study entry (Arm B). Ipi at 10 mg/kg was given by IV, every 3 weeks for 4 doses; responding or stable pts could receive maintenance ipilimumab at 10 mg/kg, every 12 weeks. Tumor assessments by modified WHO criteria were performed every 6 weeks, beginning at week 6; ORs and SD were confirmed 4 weeks after the criteria were first met. Results: The study accrued 51 pts in Arm A and 21 pts in Arm B. In Arm A, 4/51 pts had a partial response (PR) and 5/51 pts had stable disease (SD) in global lesions (brain + non-CNS) at week 12, with additional unconfirmed responses. When evaluating brain lesions only in Arm A, there were 5 PRs and 6 SDs at week 12, with additional unconfirmed responses. The duration of responses ranged from 3 to 12+ months, and duration of SD ranged from 1 to 7 months. Median global PFS was 1.9 months (95% CI, 1.2–3.0). The analysis of pts enrolled in Arm B is ongoing. There were no unexpected toxicities in either arm. CNS AEs of any grade occurred in 38 of 51 pts (74.5%) (grade 3–4 in 14 pts [27.5%]) in Arm A, and in 12 of 21 pts (57.1%) (grade 3–4 in 6 pts [28.6%]) in Arm B. The most common CNS events (> 10% of pts) of any grade were headache, dizziness, and seizures; all but one were attributable to disease. There was no association between brain edema or cerebral hemorrhage and OR. Conclusions: Ipi has a similar level of activity in brain and non-CNS lesions. This is the first study to prospectively evaluate Ipi in advanced melanoma pts with brain mets, and the data support its potential use as a treatment for these pts. The analyses are ongoing and final data will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
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