News - BCR-ABL1 Q252H

1year

Tgrx-678, a Novel Allosteric Inhibitor of BCR-ABL1, Demonstrates Preclinical Anti-Leukemia Activity, High Oral Bioavailability and Synergism with Ponatinib to Suppress the Highly Resistant Compound Mutations (ASH 2023)

ABL1 is subject to auto-inhibition mediated by myristoylation-triggered conformational change, which can be exploited to overcome resistance, as validated by allosteric inhibitors such as GNF2, GNF5 and asciminib. Furthermore, TGRX-678 and ponatinib synergize to overcome the clinically challenging resistance conferred by T315M or T315I-inclusive compound mutations. This data warrant further clinical investigation of TGRX-678 for the treatment of resistant or refractory CML patients.

1 year ago

Preclinical

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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

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BCR-ABL1 T315I • BCR-ABL1 E255K • BCR-ABL1 Y253H • BCR-ABL1 E255V • BCR-ABL1 G250E • ABL1 T315I • BCR-ABL1 Q252H • ABL1 E255K • ABL1 G250E • ABL1 Y253H • BCR-ABL1 T315M • BCR-ABL1 Y253H + BCR-ABL1 T315I

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Iclusig (ponatinib) • Scemblix (asciminib) • TGRX-678

over1year

Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older (clinicaltrials.gov)

P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2023 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2025

over 1 year ago

Trial completion date • Trial primary completion date

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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK3 (Janus Kinase 3) • CSF1R (Colony stimulating factor 1 receptor) • TSLP (Thymic Stromal Lymphopoietin)

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BCR-ABL1 E255K • BCR-ABL1 V299L • BCR-ABL1 F317L • ABL1 T315I • BCR-ABL1 L248V • BCR-ABL1 Q252H • BCR-ABL1 F317V • JAK3 mutation • ABL1 E255K • BCR-ABL1 F317C • BCR-ABL1 T315A • ABL1 F317L • BCR-ABL1 L248R

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dasatinib • Jakafi (ruxolitinib) • dexamethasone

over3years

Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older (clinicaltrials.gov)

P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2021 --> Jun 2023 | Trial primary completion date: Jun 2021 --> Jun 2023

over 3 years ago

Clinical • Trial completion date • Trial primary completion date

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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK3 (Janus Kinase 3) • CSF1R (Colony stimulating factor 1 receptor) • TSLP (Thymic Stromal Lymphopoietin)

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BCR-ABL1 E255K • BCR-ABL1 V299L • BCR-ABL1 F317L • ABL1 T315I • BCR-ABL1 L248V • BCR-ABL1 Q252H • BCR-ABL1 F317V • JAK3 mutation • ABL1 E255K • BCR-ABL1 F317C • BCR-ABL1 T315A • ABL1 F317L • BCR-ABL1 L248R

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dasatinib • Jakafi (ruxolitinib) • dexamethasone

almost4years

FINESTdm: Evaluating Efficacy and Safety of Flumatinib Versus Nilotinib for Chronic Phase Chronic Myeloid Leukemia(CML-CP) Without Optimal Response (Warning,Failure) to Imatinib or Dasatinib (clinicaltrials.gov)

P, N=200, Recruiting, Wuhan Union Hospital, China

almost 4 years ago

Clinical • New trial

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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)

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BCR-ABL1 V299L • BCR-ABL1 F317L • BCR-ABL1 M244V • BCR-ABL1 M351T • BCR-ABL1 H396R • BCR-ABL1 Q252H • BCR-ABL1 mutation • BCR-ABL1 E355G • BCR-ABL1 L387M • ABL1 F317L • ABL1 L387M • ABL1 M351T

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dasatinib • imatinib • Tasigna (nilotinib) • Hansoh Xinfu (flumatinib)

4years

[VIRTUAL] Clonal Hematopoiesis with Somatic Mutations in „AYA“ Generation of Patients with Chronic Myeloid Leukemia (ASH 2020)

In patient #6, G645delinsGWfs was found at the diagnosis and on the 3rd line nilotinib treatment...In patient #3, the CSF3R mutation A593V was found at diagnosis and confirmed 14 months after the imatinib initiation...Despite the clonal hematopoiesis with somatic mutations is considered as age-related phenomenon, in AYA CML patients, it may represent a critical problem in achieving sustained molecular response on solo TKI therapy, or even worse, it may result in higher risk of therapy failure and disease progression. Supported by MZCR 00023736

4 years ago

Clinical

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ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ATRX (ATRX Chromatin Remodeler) • CSF3R (Colony Stimulating Factor 3 Receptor) • SIRT1 (Sirtuin 1)

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BCR-ABL1 T315I • ASXL1 mutation • BCR-ABL1 E255K • BCR-ABL1 F317L • BCR-ABL1 M244V • ABL1 T315I • BCR-ABL1 M351T • BCR-ABL1 Q252H • BCR-ABL1 V379I • ABL1 E255K • ABL1 F317L • ABL1 M351T

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imatinib • Tasigna (nilotinib)

almost5years

Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older (clinicaltrials.gov)

P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2020 --> Jun 2021 | Trial primary completion date: Jun 2020 --> Jun 2021

almost 5 years ago

Clinical • Trial completion date • Trial primary completion date

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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CRLF2 (Cytokine Receptor Like Factor 2) • JAK3 (Janus Kinase 3) • CSF1R (Colony stimulating factor 1 receptor) • TSLP (Thymic Stromal Lymphopoietin)

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BCR-ABL1 E255K • BCR-ABL1 V299L • BCR-ABL1 F317L • ABL1 T315I • BCR-ABL1 L248V • BCR-ABL1 Q252H • BCR-ABL1 F317V • JAK3 mutation • ABL1 E255K • BCR-ABL1 F317C • BCR-ABL1 T315A • ABL1 F317L • BCR-ABL1 L248R

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dasatinib • Jakafi (ruxolitinib) • dexamethasone