1. Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations.
- Author
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Monga, Varun, Fadul, Camilo, Schiff, David, Taylor, Jennie, Chowdhary, Sajeel, Bettegowda, Chetan, Ansstas, George, De La Fuente, Macarena, Anderson, Mark, Shonka, Nicole, Damek, Denise, Carrillo, Jose, Kunschner-Ronan, Lara, Chaudhary, Rekha, Jaeckle, Kurt, Senecal, Francis, Kaley, Thomas, Morrison, Tara, Thomas, Alissa, Welch, Mary, Iwamoto, Fabio, Cachia, David, Cohen, Adam, Vora, Shivangi, Knopp, Michael, Dunn, Ian, Kumthekar, Priya, Sarkaria, Jann, Geyer, Susan, Carrero, Xiomara, Martinez-Lage, Maria, Cahill, Daniel, Brown, Paul, Giannini, Caterina, Santagata, Sandro, Barker, Frederick, Galanis, Evanthia, Brastianos, Priscilla, Twohy, Erin, Gerstner, Elizabeth, Kaufmann, Timothy, Iafrate, A, Lennerz, Jochen, Jeyapalan, Suriya, and Piccioni, David
- Subjects
Humans ,Focal Adhesion Protein-Tyrosine Kinases ,Meningeal Neoplasms ,Meningioma ,Mutation ,Neoplasm Recurrence ,Local - Abstract
PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS: Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.
- Published
- 2023