Alliance A071401

Alliance A071401 (NCT02523014; NCI-2015-00546) is a multicentre, genomically guided phase 2 umbrella trial for progressive or recurrent meningioma that assigns tumours to oral inhibitors by mutation: vismodegib for SMO, capivasertib for AKT1 and PIK3CA, abemaciclib for CDK pathway alterations and the focal adhesion kinase inhibitor GSK2256098 for NF2. Focal adhesion kinase inhibition has a synthetic lethal relationship with NF2 loss, the commonest driver in meningioma. This record covers the NF2 cohort, in which patients received GSK2256098 750 mg orally twice daily until progression. The coprimary endpoints were progression-free survival at six months, judged separately in grade 1 and grade 2 to 3 tumours against historical benchmarks, and response rate by Macdonald criteria; the drug counted as promising if either endpoint met its decision criterion.

Of 322 patients screened for all mutation cohorts, 36 eligible and evaluable patients with NF2 mutations were treated (12 grade 1, 24 grade 2 or 3). Across all grades one patient had a partial response and 24 had stable disease as best response. Six-month progression-free survival was 83 percent in grade 1 (10 of 12; 95 percent CI 52 to 98) and 33 percent in grade 2 or 3 (8 of 24; 16 to 55); both cohorts met the progression-free survival decision criterion. Treatment was well tolerated: seven patients had a grade 3 adverse event at least possibly related to treatment and there were no grade 4 or 5 events (Journal of Clinical Oncology 2023).

The registry lists the parent umbrella as recruiting, with an estimated enrolment of 124 and an estimated primary completion in January 2027, for the other mutation arms; the National Cancer Institute, GlaxoSmithKline, Genentech and the Brain Science Foundation are collaborators.