Alliance A071401
Alliance A071401 showed that a twice-daily tablet blocking the enzyme FAK kept more meningiomas with a faulty NF2 gene from growing at six months than history would predict, in both lower-grade and higher-grade tumours, the first mutation-matched treatment to show activity in this tumour.
Overview
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.
- 83 out of 100 people alive without the cancer growing at 6 months with GSK2256098 750 mg twice daily.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 33 out of 100 people alive without the cancer growing at 6 months with GSK2256098 750 mg twice daily.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 3 out of 100 people reached this endpoint with GSK2256098 750 mg twice daily.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- These results apply to the people the trial enrolled: Recurrent or progressive grade 1 to 3 meningioma with a somatic NF2 mutation: oral GSK2256098 750 mg twice daily until progression, as the FAK-inhibitor arm of a genomically guided Alliance phase 2 umbrella. People in a different situation may not see the same effect.
- Only 36 people took part, so the numbers are less certain than in a large trial.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
36 analysed.
10 of 12; 95% CI 52 to 98
Source8 of 24; 95% CI 16 to 55
SourceOne partial response among 36 patients (about 3%); 24 had stable disease
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival at 6 months, grade 1 NF2-mutant meningiomaprimary | GSK2256098 750 mg twice daily | 12 | 83% | - | - | link |
| Progression-free survival at 6 months, grade 2 to 3 NF2-mutant meningiomaprimary | GSK2256098 750 mg twice daily | 24 | 33% | - | - | link |
| Best response by Macdonald criteria, all gradesprimary | GSK2256098 750 mg twice daily | 36 | 3% | - | - | link |
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