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Abemaciclib for Recurrent Meningiomas with NF2 or CDK Pathway Alterations

Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trial

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Year of Publication: 2026

Journal: Nature Medicine

Citation: Nat Med. 2026;32:717–724.

Link: https://doi.org/10.1038/s41591-025-04141-4

Clinical Question

Can a CDK4/6 inhibitor shrink or stabilize progressive meningiomas harboring NF2 or CDK pathway mutations?

Bottom Line

Abemaciclib met its primary PFS6 endpoint (58%) in progressive grade 2–3 meningiomas with NF2/CDK alterations. First genomically matched systemic therapy showing activity in meningiomas.

        Major Points
        Phase 2 genomically driven trial — one arm of the Alliance A071401 umbrella study for meningiomas.
96 screened, 36 treated with abemaciclib, first 24 evaluable for co-primary endpoints.
PFS at 6 months: 58% (14/24, 95% CI 37–78%) — met success threshold of ≥8/24.
Objective response rate: 0% — no tumor shrinkage; best response was stable disease in 16/24 (67%). Suggests cytostatic mechanism.
Well tolerated: Grade 4 toxicities in only 3 patients (ALT, AST, vomiting — one each). Mean 9 treatment cycles.
First genomically matched systemic therapy showing meaningful activity in a tumor type with zero prior effective drugs.

      

Design

Study Type: Phase 2, single-arm, genomically selected

Randomization:

Blinding: None (single-arm)

Follow-up Duration: Median 21 months

Centers: 0

Countries:

Sample Size: 36

Analysis: Simon two-stage design; first 24 evaluable for primary endpoint

Inclusion Criteria

Recurrent or progressive grade 2 or 3 meningioma
Somatic NF2 mutation or CDK pathway alteration confirmed by genomic testing
Prior surgery and/or radiation
Measurable disease on MRI

Exclusion Criteria

Grade 1 meningioma
No NF2 or CDK pathway alteration
Inadequate organ function for CDK4/6 inhibitor therapy

Arms

Field	Abemaciclib
Intervention	Abemaciclib (CDK4/6 inhibitor), oral, continuous dosing
Duration	Until progression or toxicity

Outcomes

Outcome	Type	Intervention
Objective response rate (co-primary)	Secondary	0% — did not meet threshold (<3/24)
Best response — stable disease	Secondary	16/24 (67%)
Mean treatment cycles	Secondary	9 cycles
Grade 4 ALT elevation	Adverse	1/36 (2.8%)
Grade 4 AST elevation	Adverse	1/36 (2.8%)
Grade 4 vomiting	Adverse	1/36 (2.8%)
Grade 3 adverse events	Adverse	9/36

Criticisms

Single-arm design — no control group for definitive efficacy assessment
Zero objective responses — disease stabilization could reflect indolent natural history rather than drug effect
Small sample size (24 evaluable) limits statistical confidence
Genomic selection requirement limits applicability — not all meningioma patients will have NF2/CDK alterations
PFS6 is a relatively soft endpoint — overall survival data not yet mature

Funding

National Cancer Institute (Alliance). Abemaciclib provided by Eli Lilly.

Based on: Abemaciclib for Recurrent Meningiomas with NF2 or CDK Pathway Alterations (Nature Medicine, 2026)

Citation: Nat Med. 2026;32:717–724.

Content summarized and formatted by NeuroTrials.ai.

Abemaciclib for Recurrent Meningiomas with NF2 or CDK Pathway Alterations

(2026)

Objective

To evaluate abemaciclib in recurrent meningiomas with NF2 or CDK pathway alterations

Study Summary

• Abemaciclib met its primary PFS6 endpoint (58%) in progressive grade 2–3 meningiomas with NF2/CDK alterations.
• First genomically matched systemic therapy showing activity in meningiomas.

Intervention

Abemaciclib (CDK4/6 inhibitor), oral continuous dosing

Inclusion Criteria

Recurrent/progressive grade 2 or 3 meningiomas with NF2 mutations or CDK pathway alterations, after prior surgery/radiation

Study Design

Arms: Array

Patients per Arm: 36 treated, 24 evaluable

Outcome

PFS6: 58% (14/24, 95% CI 37–78%) — met threshold ≥8/24. No objective responses; best response stable disease in 16/24 (67%). Grade 4 toxicities: ALT (1), AST (1), vomiting (1).

Bottom Line

Abemaciclib met its primary PFS6 endpoint (58%) in progressive grade 2–3 meningiomas with NF2/CDK alterations. First genomically matched systemic therapy showing activity in meningiomas.

Major Points

Phase 2 genomically driven trial — one arm of the Alliance A071401 umbrella study for meningiomas.
96 screened, 36 treated with abemaciclib, first 24 evaluable for co-primary endpoints.
PFS at 6 months: 58% (14/24, 95% CI 37–78%) — met success threshold of ≥8/24.
Objective response rate: 0% — no tumor shrinkage; best response was stable disease in 16/24 (67%). Suggests cytostatic mechanism.
Well tolerated: Grade 4 toxicities in only 3 patients (ALT, AST, vomiting — one each). Mean 9 treatment cycles.
First genomically matched systemic therapy showing meaningful activity in a tumor type with zero prior effective drugs.

Study Design

Study Type: Phase 2, single-arm, genomically selected
Randomization: No
Blinding: None (single-arm)
Sample Size: 36
Follow-up: Median 21 months

Primary Outcome

Control	Intervention	HR/OR	P-value
-	58% (14/24)	-	Met threshold (≥8/24)

Limitations & Criticisms

Single-arm design — no control group for definitive efficacy assessment
Zero objective responses — disease stabilization could reflect indolent natural history rather than drug effect
Small sample size (24 evaluable) limits statistical confidence
Genomic selection requirement limits applicability — not all meningioma patients will have NF2/CDK alterations
PFS6 is a relatively soft endpoint — overall survival data not yet mature

Citation

Nat Med. 2026;32:717–724.

View Original Publication →

Abemaciclib for Recurrent Meningiomas with NF2 or CDK Pathway Alterations

Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trial

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Criticisms

Funding

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