Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations. Issue 3 (26th October 2022)

• Record Type: Journal Article
• Authors: Brastianos, Priscilla K.; Twohy, Erin L.; Gerstner, Elizabeth R.; Kaufmann, Timothy J.; Iafrate, A. John; Lennerz, Jochen; Jeyapalan, Suriya; Piccioni, David E.; Monga, Varun; Fadul, Camilo E.; Schiff, David; Taylor, Jennie W.; Chowdhary, Sajeel A.; Bettegowda, Chetan; Ansstas, George; De La Fuente, Macarena; Anderson, Mark D.; Shonka, Nicole; Damek, Denise; Carrillo, Jose; Kunschner-Ronan, Lara J.; Chaudhary, Rekha; Jaeckle, Kurt A.; Senecal, Francis M.; Kaley, Thomas; Morrison, Tara; Thomas, Alissa A.; Welch, Mary R.; Iwamoto, Fabio; Cachia, David; Cohen, Adam L.; Vora, Shivangi; Knopp, Michael; Dunn, Ian F.; Kumthekar, Priya; Sarkaria, Jann; Geyer, Susan; Carrero, Xiomara W.; Martinez-Lage, Maria; Cahill, Daniel P.; Brown, Paul D.; Giannini, Caterina; Santagata, Sandro; Barker, Frederick G.; Galanis, Evanthia;
• Is Part Of: Journal of clinical oncology. Volume 41:Issue 3(2023)
• Page Start: 618
• Page End: 628
• Publication Date: 2022-10-26
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.21.02371
• Languages: English
• ISSNs: 0732-183X

Abstract

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.