The following is a summary of “Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations,” published in the January 2023 issue of Oncology by Brastianos, et al.
Patients with meningiomas that develop or return often have few alternatives for systemic therapy. A synthetic fatal link exists between NF2 deletion and focal adhesion kinase (FAK) inhibition. In the first phase II research guided by genomics, researchers examined the effectiveness of GSK2256098, a FAK inhibitor, in grade 1-3 recurrent or progressive meningiomas, given the prevalence of NF2 mutations in these tumors.
GSK2256098, 750 mg taken twice daily, was administered to eligible individuals whose tumors tested positive for NF2i mutations. Two coprimary end points—progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria—were used to assess efficacy. PFS6 was assessed separately for grade-based subgroups of grade 1 versus 2/3 meningiomas. In accordance with the study’s design, the FAK inhibitor would be regarded as promising in this patient population if either endpoint fulfilled the relevant efficacy decision criteria.
Out of 322 patients screened for all study mutation groups, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 patients with grade 1 and 24 with grade 2 or grade 3 mutations. One patient in each grade had a partial response, and the best outcome for 24 patients was stable illness. PFS6 was seen in grade 1 patients at an 83% rate (10/12 patients; 95% CI, 52 to 98). The observed PFS6 rate in patients in grades 2 and 3 was 33% (8/24; 95% CI, 16 to 55). The groups in grades 1 and 2/3 of the research met the PFS6 efficacy end goal. Treatment was well tolerated, and there were no grade 4 or grade 5 adverse events in any of the seven patients with them.
Compared to historical controls, GSK2256098 was well tolerated and increased the PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas. Because FAK inhibition should be further examined for the patient population, the criteria for promising activity were satisfied.