Alexis Khalil

Mechanism of response to FHD-286 and decitabine combination in patients with advanced myeloid malignancies

Michael Patrick Collins, David L. Lahr, Salih Topal, Alexis Khalil et autres

ABSTRACT Impaired cellular differentiation is a defining characteristic of myeloid malignancies and remains a major therapeutic challenge. The BRG1/Brahma-associated factor (BAF) chromatin remodeling complex, through the ATPases SMARCA4 and SMARCA2, maintains the stemness of leukemic blasts and thus represents a promising target …

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Prognostic Implications of SMARCA4 , ARID1A , and Other BAF Mutations in Non‐Small Cell Lung Cancer

Alexis Khalil, Michael P. Collins, Alfonso Quintás‐Cardama

BACKGROUND AND METHODS: Non-small cell lung cancer (NSCLC) outcomes have improved remarkably with the widespread use of immune checkpoint inhibitors and small molecule inhibitors targeting driver mutations. Nevertheless, many patients continue to experience suboptimal outcomes. The prevalence of mutations in the BAF …

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Genomic and phenotypic impact of FHD-286–induced inhibition of SMARCA4/2 in patients with relapsed/refractory myeloid malignancies

David L. Lahr, Eytan M. Stein, Courtney Denton Dinardo, Ashwin Kishtagari et autres

Abstract Background: BAF complexes control chromatin accessibility to regulate gene expression programs important for cellular proliferation and differentiation. BAF activity constitutes a key dependency in several cancer types, including myeloid malignancies. FHD-286 is a first-in-class dual inhibitor of SMARCA4/2 (BRG1/BRM), the ATPase …

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Machine learning-powered integration of global proteomics and ex vivo sensitivity unveils a protein signature predictive of treatment success to AML therapy: Validation in patients treated with FHD-286, a SMARCA2/4 dual inhibitor

James T. Sorrentino, Salvador Martínez‐Bartolomé, Mahan Abbasian, Antonius Koller et autres

Abstract Acute myeloid leukemia (AML) has a 33% 5-year survival rate, and few new therapies have made a meaningful impact on the overall prognosis. A key obstacle to developing effective treatments is the lack of accurate model systems effective at capturing the …

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Supplementary Figure 13 from A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies

Courtney Denton Dinardo, Amir Tahmasb Fathi, Ashwin Kishtagari, Kapil N. Bhalla et autres

Supplementary Figure 13. Swim lane plot of responses to FHD-286 monotherapy in all patients with AML or MDS (asterisks) who had received ≥1 dose of FHD-286. AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; QD, once daily; SD, stable disease; TF, treatment failure.

Supplementary Figure 8 from A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies

Courtney Denton Dinardo, Amir Tahmasb Fathi, Ashwin Kishtagari, Kapil N. Bhalla et autres

Supplementary Figure 8. Blast percentage, hemoglobin level, leukocyte count, neutrophil count, platelet count over time, and total daily dose exposure for patient 15; R/R AML; FHD-286 10 mg QD dose group.

Supplementary Figure 1 from A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies

Courtney Denton Dinardo, Amir Tahmasb Fathi, Ashwin Kishtagari, Kapil N. Bhalla et autres

Supplementary Figure 1. Flow of patients through Study FHD-286-C-002 (monotherapy dose escalation).

Supplementary Figure 15 from A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies

Courtney Denton Dinardo, Amir Tahmasb Fathi, Ashwin Kishtagari, Kapil N. Bhalla et autres

Supplementary Figure 15. Gene expression signatures of stemness and differentiation in the blast compartment of individual patients on UMAP projection.

Supplementary Data 1 from A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies

Courtney Denton Dinardo, Amir Tahmasb Fathi, Ashwin Kishtagari, Kapil N. Bhalla et autres

Supplementary Data_ FHD-286-C-002 study protocol

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Supplementary Figure 12 from A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies

Courtney Denton Dinardo, Amir Tahmasb Fathi, Ashwin Kishtagari, Kapil N. Bhalla et autres

Supplementary Figure 12: Case 2. Peripheral blast count (top) and absolute neutrophil count (bottom) in a 25-year-old male patient with R/R treatment-related AML with KMT2A rearrangement treated with FHD286 7.5 mg QD.

Supplementary Figure 6 from A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies

Courtney Denton Dinardo, Amir Tahmasb Fathi, Ashwin Kishtagari, Kapil N. Bhalla et autres

Supplementary Figure 6. Blast percentage, hemoglobin level, leukocyte count, neutrophil count, platelet count over time, and total daily dose exposure for patient 18; R/R AML; FHD-286 7.5 mg QD dose group.

Supplementary Figure 7 from A Phase I Study of FHD-286, a Dual BRG1/BRM (SMARCA4/SMARCA2) Inhibitor, in Patients with Advanced Myeloid Malignancies

Courtney Denton Dinardo, Amir Tahmasb Fathi, Ashwin Kishtagari, Kapil N. Bhalla et autres

Supplementary Figure 7. Blast percentage, hemoglobin level, leukocyte count, neutrophil count, platelet count over time, and total daily dose exposure for patient 13; R/R AML; FHD-186 10 mg QD dose group.