Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations

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.

INTRODUCTION

Meningiomas are the most common primary brain tumor, representing 38% of all primary brain tumors.¹ Although most meningiomas can be managed primarily with surgery or radiation, a subset of meningiomas recur. Patients with progressive or recurrent meningiomas have limited treatment options after failure of surgery and radiation.² Furthermore, recurrent meningiomas are more aggressive with shorter progression-free survival (PFS) and higher likelihood of being refractory to treatment.^3-5 Historically, there have been multiple negative trials of systemic therapies in meningiomas.² Many prior trials were small and underpowered and based on a limited understanding of the molecular drivers of meningiomas.

CONTEXT

• Key Objective

• Patients with recurrent or progressive meningiomas have limited therapeutic options once surgery and radiation fail. The objective of this study was to evaluate the efficacy of focal adhesion kinase (FAK) inhibition in meningiomas, as part of the national genomically driven phase II study in meningiomas.

• Knowledge Generated

• We demonstrated that FAK inhibition with GSK2256098 resulted in an improved 6-month progression-free survival compared with historical controls in patients with meningiomas harboring somatic alterations in NF2. Furthermore, treatment with GSK2256098 was well tolerated, with no grade 4 or 5 events.

• Relevance

• As this study met its overall trial end point, FAK inhibition is worthy of further exploration for patients with recurrent or progressive meningiomas.

In the 1990s, frequent inactivating mutations in NF2 were discovered in sporadic meningiomas.^6-8 NF2 is the most commonly mutated gene in meningioma, and progressive meningiomas are enriched for NF2 mutations.^9-11 Recent advances in sequencing technologies have led to a number of seminal papers that further defined the genetic landscape of meningiomas.^9,12-16 Recurrent genetic alterations have now been described in a number of genes including AKT1, PIK3CA, and SMO, in addition to the well-established NF2 gene.^9,13 The recurrent mutations in AKT1, PIK3CA, and SMO offer potential for therapeutic targets,^17,18 as they are hotspot mutations typical of oncogenic drivers¹⁹ and are mutually exclusive from NF2 alterations.

On the basis of these data, we initiated a national genomically guided National Cancer Institute–supported Cooperative Group Trial (Alliance A071401) in patients with progressive or recurrent meningioma harboring specific mutations. The arms of the study include an AKT inhibitor for AKT- or PIK3CA-mutated meningiomas, a SMO inhibitor for SMO-mutated meningiomas, a focal adhesion kinase (FAK) inhibitor for NF2-altered tumors, and a cyclin-dependent kinase (CDK) inhibitor for CDK pathway altered tumors. We now report the results from the NF2-altered cohort and the other study arms are ongoing.

FAK inhibition with GSK2256098 for NF2-mutant meningioma was evaluated because preclinical work in mesothelioma demonstrated a strong synthetic lethal relationship with loss of merlin, the protein product of NF2.²⁰ FAK is a protein tyrosine kinase that regulates cellular proliferation, invasion, and stem-cell renewal through integrating signals from growth factor receptors and integrins.²⁰ Preclinical studies have shown that low merlin expression is predictive of sensitivity to FAK inhibition, likely because of the disruption of the weak cell-extracellular matrix or cell-cell adhesions in merlin-negative cells.²⁰ The role of FAK inhibition in meningiomas has not previously been evaluated clinically. Herein, we present the results of the FAK inhibitor arm of Alliance for Clinical Trials in Oncology trial A071401, which has now completed accrual and met the primary end point.

PATIENTS AND METHODS

Study Oversight

The study was designed by the principal investigators and conducted in accordance with the provision of the Declaration of Helsinki and Good Clinical Practice guidelines. The Central Institutional Review Board approved the Protocol (online only). All patients provided signed informed consent.

Patients

Eligible patients had histologically proven intracranial meningioma as documented by central pathology review, and measurable disease as defined by bidimensionally measurable enhancing lesions with a minimum diameter of 10 mm in both dimensions. A tumor sample from each patient underwent central genetic testing for arm determination. Presence of an NF2 alteration in the tumor tissue was required for the GSK2256098 treatment arm of the study. Patients must have had progressive or residual disease as defined by the following: residual measurable disease immediately after surgery for WHO grade 2 or 3 disease, progressive measurable disease as defined by an increase in the size of the measurable primary lesion on imaging by 25% or more in 12 months, or progressive disease after completion of radiation. For patients with residual measurable grade 1 disease immediately after surgery, progression preoperatively needed to be documented with an increase in size of the primary lesion on imaging by 25% or more in 12 months. Additional details regarding eligibility criteria are provided in the Data Supplement (online only).

Study Design, Treatment, and End Points

GSK2256098 was administered orally at 750 mg orally twice daily for a 28-day cycle until disease progression, excessive toxicity, symptomatic neurologic deterioration, or study consent withdrawal. Details regarding dose reductions are provided in the Data Supplement.

Contrast-enhanced brain magnetic response imaging was obtained every 8 weeks for restaging using a consensus magnetic response imaging protocol.²¹ The coprimary end points were 6-month progression-free survival (PFS6) and response rate (RR) as determined using Macdonald criteria²² by local investigator review. PFS6 was defined as the number of patients not having progressive disease or death within 6 months of the first day of treatment divided by the total number of evaluable patients. RR was defined as the number of responses divided by the total number of evaluable patients. A patient was deemed to have a response if they had a confirmed partial response (PR) or complete response.

Statistical Analysis

This is a prospective, one-stage, multiarm phase II study evaluating the efficacy of targeted therapies in patients with specific mutations. Each of the mutation groups in this trial is evaluated in parallel with a separate phase II study design. Herein we are reporting the results of the FAK inhibitor treatment arm. Within each arm defined by tumor mutation and inhibitor, there are two different patient cohorts included on the basis of histology: grade 1 versus 2/3 meningiomas. Efficacy was evaluated using two coprimary end points: RR and PFS6. To accommodate these two coprimary end points and their simultaneous evaluation for a given treatment arm, a Bonferroni correction²³ was used to further constrain the one-sided type I error (bounded at 5% per arm). The RR end point was powered and evaluated across all patients regardless of grade for the given study arm (α = .012). The PFS6 end point was calculated and powered as a proportion and evaluated within each grade cohort (nested within each arm; grade 1: α = .014, grade 2/3: α = .020). Power calculations were performed with EAST v6.3 and PASS 15.01. Per study design, the treatment would be considered promising in the mutation group for this patient population if the decision criteria for either end point were met.

For the GSK2256098 treatment arm reported here, a total of 36 evaluable patients were required to provide at least 94% power to detect a true RR of at least 20%, with a significance level of 0.013 against the null hypothesis of a true RR of 2.5%. For this end point, the agent would be considered worthy of further testing in this mutation-defined treatment arm if at least four responses (ie, ≥ 11.1%) were observed among the 36 evaluable patients. For the PFS end point within the grade 2/3 cohort of the GSK2256098 treatment arm, a total of 24 evaluable patients provided at least 85% power to detect a true PFS6 rate of at least 41.5%, with a significance level of 0.02 against the null hypothesis that the true PFS6 rate was 15%. If at least 8 of these 24 evaluable patients (at least 33.3%) were progression-free and alive at 6 months, the agent would be considered worthy of further testing in this mutation-defined grade 2/3 cohort. Within the grade 1 cohort, a total of 12 evaluable patients provided at least 79% power to detect a true PFS6 rate of at least 65%, with a significance level of 0.014 against the null hypothesis of 25% PFS6 rate. Here, if at least 7 of the 12 evaluable patients (at least 58%) demonstrated PFS6, the agent would be considered worthy of further testing in this mutation-defined grade 1 cohort. The null hypotheses for each of the grade-based subgroups described above were based on historical benchmark data obtained from a systematic review of prior published reports of medical therapies in meningiomas,² where PFS6 was 23%-29% in grade 1 meningioma and 0%-29% in trials of grade 2/3 meningiomas, with 14% as the median across most trials of grade 2/3 meningioma. The first 12 (grade 1 cohort) and 24 (grade 2/3 cohort) patients who met the eligibility criteria, signed the consent form, and began treatment were considered evaluable for the safety end points as well as secondary and exploratory end points. Patients also had to have had evaluable imaging data unless they died within the first 6 months of study entry to be included in the primary end point analysis.

The secondary end points, overall survival and progression free-survival, were summarized for each cohort within each treatment arm with Kaplan-Meier²⁴ curves and estimates. PFS is a time-to-event outcome defined as the time from initiation of treatment to the time of progression and/or death. Patients who were alive and progression-free at the time of their last evaluation were censored at that time point. No formal comparisons were made between the grade cohorts. An additional secondary end point was the rate of adverse events (AEs) in each cohort. AEs were graded by the site investigators according to CTCAE Version 4.0 and were summarized as the number and graded severity of each AE by type as well as aggregated and summarized by incidence of any AE, any AEs grade 3 or greater, and any AEs grade 4 or greater. Additional details regarding data collection, monitoring, and analysis are provided in the Data Supplement.

Targeted Molecular Profiling

Molecular profiling was carried out as described in the Data Supplement.^25-29

RESULTS

Patients

A total of 322 patients were screened for all mutation cohorts of the study; 101 patients were preregistered to the study while the GSK2256098 treatment arm was open and 38 patients were enrolled to the GSK2256098 arm. Between August 28, 2015, and May 18, 2016, and between April 14, 2017 and July 19, 2017, 12 patients were enrolled to the WHO grade 1 cohort and 26 to the WHO grade 2/3 cohort (Fig 1). One grade 2/3 patient was deemed ineligible upon centralized review. Another patient received one cycle of therapy and went off study treatment because of grade 3 AST and grade 3 ALT (both deemed probably related to study treatment). Since no scans beyond baseline were available on this patient for the first year, they were not considered evaluable for the primary end points; this patient is still included in safety and baseline characteristic summaries. Thus, there were 12 grade 1 and 24 grade 2/3 patients evaluable for the coprimary end points (Table 1). Across all 37 eligible patients who received treatment on this study, the median age at study enrollment was 64 years (range, 22-76 years) and 18 were male (48.6%; Table 1). The majority of patients (33/37 = 89.2%) had an Eastern Cooperative Oncology Group performance status of 0 or 1 at study entry. All patients had received surgery related to their meningioma, 29 patients (78.4%) had received radiation therapy for their tumor, and 12 patients (32.4%) had received prior systemic therapy (Table 1). Twenty-eight patients (75.7%) received at least two prior treatment modalities.

FIG 1.

CONSORT diagram of patient population. ^aEighty-nine patients were identified as having NF2 mutation while the NF2 arm was opened to accrual and 12 were allowed to be registered while the NF2 arm was closed to accrual as they were already in preregistration. From May 8, 2016 to April 14, 2017 (when the NF2 arm closed to accrual for grade 2/3 tumors), NF2 mutation testing was performed if the patient had a grade 1 tumor. ^bBecause of having resection after registration and tumor was multifocal. ^cOne grade 2/3 cohort patient received only one cycle of treatment, then went off study treatment because of grade 3 AST and grade 3 ALT (both deemed probably related to study treatment). This patient had a baseline scan and no other scans until 1 year from study entry (because of patient follow-up visits cancellations) and was excluded from primary end point analysis. End of study treatment reasons (all enrolled patients): 1 grade 1 cohort patient and 3 grade 2/3 cohort patients withdrew/refused further treatment, 3 grade 1 cohort patients and 1 grade 2/3 cohort patient ended study treatment because of adverse events/side effects/complications, and 8 grade 1 cohort patients and 21 grade 2/3 cohort patients ended study treatment because of disease progression. One grade 2/3 cohort patient remains in study treatment 4 years from study initiation.

TABLE 1.

Patient Characteristics

Efficacy

In the grade 1 cohort, patients received a median of 11 treatment cycles and in the grade 2/3 cohort, four cycles (Data Supplement). At 6 months, 10 of 12 grade 1 patients (83%) and 8 of 24 (33%) grade 2/3 patients were progression-free and alive (Table 2). The best response was stable disease in 10 (83%) grade 1 and 14 (58%) grade 2/3 patients and PR in one grade 2/3 (4%) patient (Table 3). The decision rule was not met for RR, with only one PR observed in a grade 2/3 cohort patient with a 5.5-month duration of response. The PFS6 efficacy end point criteria were met for both grade-based cohorts and thus met the overall criteria for the FAK inhibitor to be considered promising in each of the cohorts. One patient still remains on treatment 4 years after starting on study. The median overall survival has not yet been reached for grade 1, and was 21.5 months (95% CI, 14.8 to 38.0) for grade 2/3 patients (Fig 2A). The median PFS was 12.8 months (95% CI, 9.2 to not reached) for grade 1 patients and 3.7 months (95% CI, 3.6 to 7.2) for grade 2/3 patients (Fig 2B). In a secondary analysis, the Alliance Imaging Central Lab centrally reviewed all images for 33 patients, where the remaining three patients did not have films available for central review (Data Supplement).

TABLE 2.

PFS at 6 Months

TABLE 3.

Best Response (Macdonald criteria)

FIG 2.

KM curves of OS and PFS for patients treated with GSK2256098. (A) KM curve of OS (note that a total of 13 censors were observed after month 30). The median OS for the grade 1 cohort was not yet reached and for the grade 2/3 cohort was 21.5 months. (B) KM curve of PFS. The median PFS was 12.8 months for the grade 1 cohort and 3.7 months for the grade 2/3 cohort. KM, Kaplan-Meier; NE, not evaluable; OS, overall survival; PFS, progression-free survival.

Toxicity

Five patients across both cohorts (13.9%) had dose modifications in at least once cycle (Data Supplement). Four patients were taken off study because of AEs, side effects, or complications (Data Supplement). Fifteen patients had grade 3 events regardless of attribution and seven patients had treatment-related grade 3 events (Data Supplement). Grade 3 AEs at least possibly related to treatment included proteinuria, pain, lymphopenia, rash, nervous system disorder, ALT/AST elevation, cholecystitis, and hypertriglyceridemia (Table 4).

TABLE 4.

Listing of Grade 3+ AEs Max Grade per Patient per Event at Least Possibly Related Number of Evaluable Patients: 37

Exploratory Analyses

In an exploratory analysis, when data were available (n = 10), we calculated pretreatment growth rates (Data Supplement). Those patients who were progression-free and alive at 6 months had an observable decline in their tumor growth rates in relation to the tumor growth rates observed in the 6 months before study entry. Changes in tumor size on treatment were also evaluated across all patients (Data Supplement). Seven patients with grade 1 tumors had observed reductions in tumor areas that did not meet criteria for PR, and nine with grade 2/3 tumors had observed reductions in tumor area, one of which met criteria for PR (Data Supplement). We did not detect a statistically significant difference in baseline tumor area measurements between those patients who were classified as progression-free and alive at 6 months and those who progressed at 6 months (Data Supplement).

Molecular profiling of all tumor samples using targeted next-generation sequencing was also carried out, which included genes implicated as being frequently altered and/or prognostic in meningioma including alterations in CDKN2A, TERT promoter, SMARCB1, SMO, AKT, PIK3CA, and PTEN (Fig 3 and Data Supplement). We evaluated whether specific genetic mutations correlated with clinical outcomes. Notably, we did not detect an association between PFS6 and mutational status of CDKN2A or TERT promoter (Data Supplement), both of which have been described to correlate with poor prognosis and progression in meningiomas.^5,30-33

FIG 3.

Mutational landscape in meningioma trial patients. CoMut plot displaying grade, genetic variants, and best response at 6 months. The top and side histograms (green) represent total number and fraction of reported variants per sample or gene, respectively. For a detailed list of variant annotations, see the Data Supplement. CoMut plot, Comutation plot; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease.

DISCUSSION

Approximately 33,000 meningiomas are diagnosed each year.¹ The management of recurrent and progressive meningioma represents an enormous unmet need in neuro-oncology. Recurrent meningiomas can have significant morbidity and mortality, and have no effective medical therapy when surgery and radiation have failed. There has been a paucity of trials for meningiomas, which has further limited our ability to investigate the efficacy of therapeutic agents in this disease. The advent of improved sequencing technologies has led to an enhanced understanding of the molecular underpinnings driving meningiomas. We now know that meningiomas are characterized by distinct, mutually exclusive genetic subgroups.^{9,12-16,30,34-36} To that end, to our knowledge, we conducted the first national genomically guided trial for this disease under the auspices of Alliance for Clinical Trials in Oncology. We demonstrated that this study design is feasible in a multicenter setting for this patient population. Importantly, FAK inhibition with GSK2256098 was well tolerated, with no grade 4 or 5 toxicities, and was associated with an improvement in PFS6 compared with historical controls.

Historically, targeting tumor suppressors, such as NF2, has been therapeutically challenging. Inhibition of FAK in NF2-mutated meningiomas clinically leveraged the concept of synthetic lethality, whereby loss of a tumor suppressor increases the efficacy of pharmacologically inhibiting another gene product.²⁰ This is analogous to poly(adenosine diphosphate-ribose) polymerase inhibition in tumors harboring mutations in BRCA1 or BRCA2.^37,38 We demonstrate for the first time, to our knowledge, that this is a promising therapeutic approach in meningiomas. These data complement analogous results suggesting that GSK2256098 has clinical activity in patients with mesothelioma with merlin loss.³⁹

We chose PFS6 and RR as coprimary end points because an improvement in either of these end points would be clinically meaningful for this patient population as there are no standard medical therapies. As such, the type I error for this study was tightly controlled to limit the likelihood of false-positive results and to further support our ability to evaluate the two clinical outcomes of interest for this patient population. One of the major challenges with designing trials in meningiomas is that previously conducted trials do not use consistent end points or uniform response criteria. A response assessment in neuro-oncology (RANO) systematic review of 47 prior studies of medical therapy in meningioma composed of 164 patients was conducted to carefully define the clinical course and benchmarks for overall survival, PFS, and PFS6; on the basis of recommendations from this systematic review, we chose PFS6 as one of the end points.² The null hypotheses for each of the grade-based subgroups were based on the historical data obtained from this previously published RANO review,² where PFS6 was reportedly 23%-29% in grade 1 meningioma and 0%-29% in trials of grade 2/3 meningiomas, with 14% as the median across most trials of grade 2/3 meningioma. Since the publication of this RANO review, recent clinical trials for patients with meningiomas have used PFS6 as a primary end point with similar null hypotheses as used in A071401.^40,41 The null hypothesis for RR was selected because RR has been close to 0% in the majority of studies of systemic therapies in recurrent or progressive meningiomas.² We demonstrated that the clinical benefit of GSK2256098 was primarily accomplished through stabilization of the meningioma and inhibition of growth: disease stability is clinically meaningful for this heavily pretreated patient population.

Toxicity of medical therapy is an important consideration for patients with meningioma who potentially could stay on therapy for prolonged periods of time. GSK2256098 was well tolerated with only seven patients experiencing grade 3 treatment-related AEs and none having grade 4 or 5 AEs. As the effect of long-term medical therapies on quality of life in meningiomas is an understudied area, future studies could benefit from more detailed neurocognitive evaluations and patient-reported outcomes to evaluate the impact of GSK2256098 on neurocognition and quality of life.

The study has some limitations. First, this was a small phase II study comparing to historical controls and not a randomized controlled trial. However, given the possible accrual challenges frequently encountered in trials for uncommon brain tumors, our goal was to limit the sample size, while powering the study to detect a promising signal. Before this study, there was no precedent for a national precision medicine trial in rare primary brain tumors using an umbrella approach where patients are assigned to treatment arms on the basis of molecular characteristics. In addition, the majority of prior meningioma trials of medical therapy have had very small patient numbers. Our objective was to design a trial that could be conducted within a reasonable time frame to demonstrate both that a genomically guided trial was feasible in this patient population and that this approach could swiftly guide the development of effective novel therapies for meningioma. To this end, we used the end point of PFS6 and historical control data as recommended by the recent RANO systematic review, which is becoming standard for the field of meningiomas.^2,40-42 Second, given the requirement for tissue, all patients needed a surgical intervention before this study. Future studies can benefit from the identification of noninvasive biomarkers such cell-free DNA for the detection of clinically actionable mutations,⁴³ as this would also enable a neoadjuvant approach in meningiomas as well as facilitate assessment of response to treatment.

In conclusion, we present the results of an umbrella, genomically driven clinical trial design for patients with meningioma focusing on the investigation of the efficacy of FAK inhibition in patients with NF2-mutated meningiomas. The trial met its overall trial end point, confirming that FAK inhibition is worthy of further exploration in patients with meningioma both in preclinical and clinical studies. Further investigation to evaluate FAK inhibition in combination with other compounds is also warranted. Trials evaluating the efficacy of agents such as dual mTOR inhibitors in NF2-driven meningioma are also being conducted and are preliminarily showing encouraging results.⁴² Data from these trials may pave the way for promising combinatorial approaches for the management of patients with meningioma.

Additional arms of this novel genomically guided clinical trial are actively accruing. As more data emerge from this and other trials, precision medicine approaches are expected to be integrated into meningioma treatment paradigms.

DATA SHARING STATEMENT

Deidentified patient data may be requested from Alliance for Clinical Trials in Oncology via concepts@alliancenctn.org.

AUTHOR CONTRIBUTIONS

Conception and design: Priscilla K. Brastianos, Erin L. Twohy, A. John Iafrate, Suriya Jeyapalan, Sajeel A. Chowdhary, Michael Knopp, Priya Kumthekar, Daniel P. Cahill, Paul D. Brown, Caterina Giannini, Sandro Santagata, Evanthia Galanis

Financial support: Priscilla K. Brastianos, A. John Iafrate

Administrative support: Priscilla K. Brastianos, A. John Iafrate, Sajeel A. Chowdhary, Michael Knopp, Sandro Santagata

Provision of study materials or patients: Priscilla K. Brastianos, A. John Iafrate, Jochen Lennerz, Varun Monga, Camilo E. Fadul, David Schiff, Sajeel A. Chowdhary, George Ansstas, Mark D. Anderson, Nicole Shonka, Denise Damek, Rekha Chaudhary, Thomas Kaley, Tara Morrison, Fabio Iwamoto, David Cachia, Adam L. Cohen, Shivangi Vora, Ian F. Dunn, Sandro Santagata, Evanthia Galanis

Collection and assembly of data: Priscilla K. Brastianos, Erin L. Twohy, Timothy J. Kaufmann, A. John Iafrate, Jochen Lennerz, Suriya Jeyapalan, David E. Piccioni, Camilo E. Fadul, David Schiff, Jennie W. Taylor, Sajeel A. Chowdhary, Chetan Bettegowda, George Ansstas, Macarena De La Fuente, Mark D. Anderson, Denise Damek, Jose Carrillo, Lara J. Kunschner-Ronan, Kurt A. Jaeckle, Francis M. Senecal, Thomas Kaley, Tara Morrison, Alissa A. Thomas, Mary R. Welch, Fabio Iwamoto, David Cachia, Adam L. Cohen, Shivangi Vora, Michael Knopp, Priya Kumthekar, Xiomara W. Carrero, Maria Martinez-Lage, Caterina Giannini, Sandro Santagata

Data analysis and interpretation: Priscilla K. Brastianos, Erin L. Twohy, Elizabeth R. Gerstner, Timothy J. Kaufmann, Jochen Lennerz, Suriya Jeyapalan, David E. Piccioni, Varun Monga, Camilo E. Fadul, David Schiff, Sajeel A. Chowdhary, Nicole Shonka, Jose Carrillo, Rekha Chaudhary, Fabio Iwamoto, Ian F. Dunn, Jann Sarkaria, Susan Geyer, Xiomara W. Carrero, Daniel P. Cahill, Caterina Giannini

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations

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