^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

ABL1 T315I

i
Other names: ABL proto-oncogene 1, ABL, c-ABL, JTK7, p150, ABL1
Entrez ID:
3d
Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the T315I mutation after ≥1 prior tyrosine kinase inhibitor: 2-year follow-up results. (PubMed, Leukemia)
Five (10.4%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib's effectiveness, including in almost 50% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP.
Journal
|
ABL1 (ABL proto-oncogene 1)
|
BCR-ABL1 T315I • ABL1 T315I
|
Iclusig (ponatinib) • Scemblix (asciminib)
10d
Ponatinib-review of historical development, current status, and future research. (PubMed, Am J Hematol)
Ponatinib-based therapy also resulted in significantly better outcomes in frontline Ph-positive ALL compared with prior TKIs and is becoming a new standard of care in this setting. As the clinical development of third-generation TKIs and their rational combinations progresses, we envision further transformative changes in the treatment of CML and Ph-positive ALL.
Review • Journal
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I
|
Iclusig (ponatinib)
11d
Ponatinib vs Imatinib in Frontline Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. (PubMed, JAMA)
The safety profile of ponatinib was comparable with imatinib. ClinicalTrials.gov Identifier: NCT03589326.
Clinical • Journal
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I
|
imatinib • Iclusig (ponatinib)
1m
Journal
|
ABL1 (ABL proto-oncogene 1) • ITGA6 (Integrin, alpha 6) • ITGB1 (Integrin Subunit Beta 1) • ITGB4 (Integrin Subunit Beta 4)
|
ABL1 T315I
|
imatinib
1m
The molecular signature of BCR::ABLP210 and BCR::ABLT315I in a Drosophila melanogaster chronic myeloid leukemia model. (PubMed, iScience)
We identified six genes that were consistently upregulated in the fly CML model and validated in adult and pediatric CML patients and in a mouse cell line expressing BCR::ABL1T315I. This study provides a comprehensive analysis of gene signatures in BCR::ABL1p210 and BCR::ABL1T315I, laying the groundwork for targeted investigations into the role of these genes in CML pathogenesis.
Journal
|
ABL1 (ABL proto-oncogene 1)
|
BCR-ABL1 T315I • ABL1 T315I • BCR expression
2ms
Characterization of Asciminib-Resistant Philadelphia Chromosome-Positive Cells. (PubMed, World J Oncol)
Y139D and T315I mutations are extremely resistant to asciminib. Ponatinib and omacetaxine show potential for treating asciminib-resistant chronic myeloid leukemia.
Journal
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I
|
Iclusig (ponatinib) • Scemblix (asciminib) • Synribo (omacetaxine mepesuccinate)
3ms
A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov)
P1/2, N=68, Active, not recruiting, Takeda | Trial completion date: Aug 2027 --> Jan 2027 | Recruiting --> Active, not recruiting
Enrollment closed • Trial completion date
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IGH (Immunoglobulin Heavy Locus) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor) • PIAS4 (Protein Inhibitor Of Activated STAT 4)
|
BCR-ABL1 fusion • BCR-ABL1 T315I • ABL1 T315I • BCR-ABL1 mutation
|
cytarabine • Iclusig (ponatinib) • cyclophosphamide
3ms
Quantitative detection of T315I mutations of BCR::ABL1 using digital droplet polymerase chain reaction. (PubMed, Hematol Transfus Cell Ther)
T315I mutations have a high incidence in Ph-positive ALL patients even if the course of disease is short. In molecular biology, T315I mutation detection is indicated for CML patients not in remission.
Journal • Polymerase Chain Reaction • Tumor mutational burden
|
TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I • ABL1 fusion
4ms
Spectrum of BCR-ABL mutations in Azerbaijanian imatinib-resistant patients with chronic myeloid leukemia. (PubMed, Pathol Oncol Res)
Overall survival (OS) of the patients with BCR-ABL1 mutations was significantly lower comparing to the patients with no mutation (p < 0.05) and 8 patients with T315I mutation presented OS of 0%. T315I was the most commonly identified BCR-ABL1 mutation in TKI-resistant CML patients of Azerbaijani origin, being associated with disease progression and poor OS.
Journal
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
ABL1 T315I • BCR-ABL1 mutation
|
imatinib
5ms
How to Manage Philadelphia-Positive Acute Lymphoblastic Leukemia in Resource-Constrained Settings. (PubMed, Cancers (Basel))
The T315I mutation is the most common mechanism for disease resistance, being targetable to ponatinib. Blinatumomab, a bispecific antibody, has shown significant synergy with TKIs in treating this disease. It serves as an excellent salvage therapy, aside from achieving outstanding results when incorporated into the frontline.
Review • Journal
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IKZF1 (IKAROS Family Zinc Finger 1)
|
ABL1 T315I
|
Iclusig (ponatinib) • Blincyto (blinatumomab)
6ms
Good Survival of CAR-T Cell Therapy Bridging to Allo-HSCT for Relapsed/Refractory Ph-Positive B-Cell Acute Lymphoblastic Leukemia (ASH 2023)
Myeloablative conditioning regimens with total body irradiation (fractionated, total 10 Gy) /etoposide (200mg/m 2 x 3) /fludarabine (30mg/m 2 x 5) or cyclophosphamide (1...Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis... Our results indicate that CAR-T bridging to allo-HSCT is safe and effective for patients with r/r ph+ ALL. The 2 years OS and LFS both reach to 78. 6%.
CAR T-Cell Therapy • IO biomarker
|
ABL1 (ABL proto-oncogene 1) • CD34 (CD34 molecule)
|
ABL1 T315I
|
cyclophosphamide • etoposide IV • methotrexate • fludarabine IV
6ms
ASC2ESCALATE: A US Phase 2, Open-Label, Single-Arm, Dose-Escalation Study of Asciminib (ASC) Monotherapy in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) As Second-Line (2L) and First-Line (1L) Treatment (ASH 2023)
Also, with >2 years of follow-up, ASC demonstrated superior efficacy and better safety and tolerability compared with bosutinib in pts with CML-CP without the T315I mutation after ≥2 prior TKIs in the phase 3 ASCEMBL study (NCT03106779)...In addition to pts receiving ASC as their 2L TKI, a separate cohort of newly diagnosed pts will be included, and these pts may receive up to 4 weeks of prior treatment with imatinib or an approved second-generation TKI (Table)...Dose escalation of ASC in 2L and 1L is another treatment strategy and results from ASC2ESCALATE will add to the growing body of evidence for using ASC to treat pts with CML-CP. Recruitment for pts using ASC as their 2L TKI began November 2022, and as of July 10, 2023, 5 pts have been enrolled in this cohort; Up to 92 and 90 pts are estimated to enroll in the 2L and 1L cohorts, respectively, across 90 sites.
Clinical • P2 data
|
ABL1 T315I
|
imatinib • Bosulif (bosutinib) • Scemblix (asciminib)
6ms
Asciminib Enhances Its Treatment Efficacy Synergistically in the Treatment of Chronic Myeloid Leukemia Harboring ABL1 Kinase Domain Mutation When Combined with a Reduced Dose of Ponatinib, Dasatinib, or Bosutinib, but Not with Nilotinib or Imatinib (ASH 2023)
The present study demonstrated that a half of baseline conc ABPIs in combination with ASC is as effective as other ABPIs not just in WT but also in other ABL1 KDM CML cell lines. Different CML cell lines harboring different ABL KDM has different treatment spectrum on optimal ABPI drug as well as optimal drug conc. This result will be useful to design future clinical trial of dual blockade of ASC with other ABPIs considering the ABL KDM profiles.
Clinical
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
BCR-ABL1 E255K • BCR-ABL1 F317L • BCR-ABL1 G250E • BCR-ABL1 M244V • ABL1 T315I • BCR-ABL1 M351T • BCR-ABL1 H396P • BCR-ABL1 Y253F • BCR-ABL1 F317V • ABL1 E255K • BCR-ABL1 T315A • ABL1 F317L • ABL1 G250E • ABL1 M351T
|
dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Scemblix (asciminib)
6ms
ASC4KIDS: A Multicenter, Open-Label, Phase Ib/II Study to Determine the Dose and Safety of Asciminib in Pediatric Patients with Chronic Myeloid Leukemia in the Chronic Phase (ASH 2023)
2% at week 24) and a favorable safety profile compared with bosutinib 500 mg once daily (qd) in adult patients with Ph+ CML-CP in the phase 3 ASCEMBL study (NCT03106779). The study is still recruiting. This study will determine a pediatric dose for asciminib and support a strategy of full extrapolation from adult data to use in the pediatric patients with CML-CP.
Clinical • P1/2 data
|
ABL1 (ABL proto-oncogene 1)
|
BCR-ABL1 T315I • ABL1 T315I
|
Bosulif (bosutinib) • Scemblix (asciminib)
6ms
Propensity Score Matching Comparing Asciminib Versus Ponatinib in Chronic Myeloid Leukemia Patients Who Failed Prior Tyrosine Kinase Inhibitor Therapy (ASH 2023)
Background ASCEMBL trial has demonstrated superior efficacy of Asciminib (ASC) over Bosutinib in terms of molecular response, and event-free survival. These findings contribute valuable insights to the understanding of ASC and PON treatments in pts with specific disease characteristics and may have implications for personalized therapy decisions in the absence of clinical trials comparing these drugs. Our aim is to expand our PSM cohort.
Clinical
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I
|
Iclusig (ponatinib) • Bosulif (bosutinib) • Scemblix (asciminib)
6ms
Efficacy and Safety of Asciminib in Chinese Patients with Philadelphia Chromosome(Ph)-Positive Leukaemias (ASH 2023)
Its efficacy and safety profile in patients with chronic-phase chronic myeloid leukaemia (CML) have been shown in the Phase 3 ASCEMBL study, comparing asciminib 40 mg twice daily versus bosutinib 500 mg once daily...All had received prior chemotherapy in combination with a TKI (imatinib, N=3; dasatinib, N=5; ponatinib, N=5), with 3 patients having undergone allogeneic haematopoietic stem cell transplantation (allo-HSCT)...ConclusionAsciminib demonstrated promising clinical efficacy with satisfactory tolerance in this cohort of Ph+ leukaemias failing multiple lines of therapy. Further investigation of its therapeutic role in Ph+ ALL is warranted.
Clinical
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I • ABL1 E255K
|
dasatinib • imatinib • Iclusig (ponatinib) • Bosulif (bosutinib) • Scemblix (asciminib)
6ms
Treatment-Free Remission in Ponatinib-Treated CML Patients: The Italy-Tfr Experience (ASH 2023)
First-line therapy was available for 16 pts and was imatinib for 11 pts, nilotinib for 2 pts, dasatinib for 3 pts. Our data confirmed the efficacy of ponatinib in second or later lines of treatment. All pts, including those treated for resistance, achieved optimal responses at 3 mos. We also showed that TFR may be feasible for some pts treated in second or subsequent lines, not only for intolerance.
Clinical
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I • ABL1 F359V • ABL1 Y253H
|
dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib)
6ms
In Vitro Evidence of Synergistically Enhanced Efficacy of Axitinib When Combined with Asciminib in T315I Mutated Chronic Myeloid Leukemia (ASH 2023)
T315I mutation in ABL KD confers broad-spectrum resistance to all 1st- and 2nd-generation ABPIs including Imatinib (IMA), Dasatinib (DAS), Nilotinib (NIL) and Bosutinib (BOS). This result suggests synergistically enhanced inhibitory activity of dual blockade using AXI combined with ASC specifically for T315I mutant CML. This approach will be promising against CML cells carrying compound mutation with T315I mutation, which is highly resistant even to Ponatinib or Asciminib.
Preclinical
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I
|
dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Inlyta (axitinib) • Scemblix (asciminib)
6ms
Olverembatinib (HQP1351) Combined with Chemotherapy Is an Effective and Safe Treatment in Patients with Philadelphia Chromosome-Positive (Ph +) Acute Lymphoblastic Leukemia (ALL) and Chronic Myeloid Leukemia in Lymphoid Blast Phase (CML-LBP) That Failed TKI-Based Regimens (ASH 2023)
The 15 R/R patients (11, Ph + ALL; 4, CML-BP) received olverembatinib 30 or 40 mg on alternate days combined with VP (vindesine 4 mg once per week for 4 weeks and prednisone 1 mg/kg for 3 weeks and tapered at the fourth)...Among the 16 patients with molecular resistance to TKI-based chemotherapy (imatinib [n = 4]; dasatinib [n = 9]; flumatinib [n = 3]), 2 received olverembatinib monotherapy, 7 olverembatinib plus VP, and 7 hyper-CVAD, of whom 8 received subsequent allogeneic transplantation...Treatment-related nonhematologic severe adverse events were observed in 3 patients, including (each) stable angina pectoris, severe pneumonia, and fatal Klebsiella sepsis. Conclusions Olverembatinib-based chemotherapy is effective and safe in patients with R/R and molecular resistant Ph + ALL or CML-LBP.
Clinical
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I • ABL1 E255K • ABL1 F317L • ABL1 G250E • ABL1 M351T • ABL1 Y253H
|
dasatinib • imatinib • Nailike (olverembatinib) • Hansoh Xinfu (flumatinib) • vindesine
6ms
The Promising Third-Generation TKI Olverembatinib in Adult BCR: : ABL1-Positive Acute Lymphoblastic Leukemia with T315I Mutation and Relapsed/Refractory Disease (ASH 2023)
As for the 23-year-old female pt with CML-LBP, dasatinib was switched to olverembatinib when T315I, E255K, and E255V mutations were detected...At present, the patient maintained in CR, and blinatumomab will be used for MRD clearance before allo-HSCT...In addition, bridging allo-HSCT after deeper molecular remission could further improve survival. The safety profiles were manageable, but there is still a need to explore the optimal dose in elderly pts.
Clinical
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
BCR-ABL1 E255K • BCR-ABL1 E255V • ABL1 T315I • ABL1 E255K • BCR-ABL1 T315I + ABL1 E255V
|
dasatinib • Blincyto (blinatumomab) • Nailike (olverembatinib)
6ms
The Efficacy and Safety of the Third Generation TKI Olverembatinib in Adult Ph+ Acute Lymphoblastic Leukemia with Relapsed Disease or Persistent MRD Bridging to Allo-HSCT: A Case Series from a Single Center (ASH 2023)
The Olverembatinib involving regimen included: Olverembatinib and Venetoclax in combination with VP based low intensive chemotherapy (Vindesine /Prednisone), Olverembatinib+Blinatumomab, Olverembatinib + INO. ConclusionThis work suggests that Olverembatinib showed a profound response rate and was well tolerated in MRD clearance prior to allo-HSCT in Ph+ALL with disease recurrence and persistently MRD positive. Larger prospective studies are needed.
Clinical
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
BCR-ABL1 G250E • ABL1 T315I • ABL1 G250E
|
Venclexta (venetoclax) • Blincyto (blinatumomab) • Nailike (olverembatinib) • vindesine
6ms
A Phase II Study of Flumatinib with Chemotherapy for Newly Diagnosed BCR: : ABL1-Positive Acute Lymphoblastic Leukemia in Adults: Updated Results from RJ-ALL2020.2A Trial (ASH 2023)
It has shown better efficacy compared to imatinib in clinical trials of CML, but few reports are available in ALL...Once the diagnosis is confirmed, the combination of flumatinib (600mg/day) and VIP-based chemotherapy regimen (Vincristine/Idarubicin/Prednisone) is given promptly...Blinatumomab is allowed to administer for MRD clearance before allo-HSCT...Achieving MRD flow negativity or CMR at 3 months and bridging allo-HSCT could further improve survival. The long-term follow-up data will be disclosed soon.
Clinical • P2 data
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
ABL1 T315I
|
imatinib • Blincyto (blinatumomab) • vincristine • idarubicin hydrochloride • Hansoh Xinfu (flumatinib)
6ms
The Efficacy and Safety of Olverembatinib Combined with Monoclonal Antibodies As Salvage Therapy for RR B ALL with ABL1 Fusion Gene Positive (ASH 2023)
Recently, such pts have new hope with the wide application of a novel third-generation TKI Olverembatinib developed in China and Blinatumomab(CD19 antibody,BITE)and INOTUZUMAB OZOGAMICIN(CD22 antibody,Ino. For heavily treated RR ABL1+B ALL pts,including those after treatment with ponatinib and other TKICART and HSCT, Olverembatinib combined with monoclonal antibodies is effective and safe. In my cases, it is particularly noteworthy that one pts ,Ph like ALL with ABL1 FG, received Olverembatinib combination BITE and achieved a surprising response, so Olverembatinib may also be effective and safe for such pts. In addition, venetoclax may be used as a sensitizer for TKI or other antitumor drugs.
Clinical
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • CD22 (CD22 Molecule)
|
CD19 expression • ABL1 T315I • CD22 expression • ABL1 fusion
|
Venclexta (venetoclax) • Iclusig (ponatinib) • Blincyto (blinatumomab) • Besponsa (inotuzumab ozogamicin) • Nailike (olverembatinib)
6ms
Olverembatinib (HQP1351) Enhances Antitumor Effects of Chemotherapy in Philadelphia Chromosome-Positive (Ph⁺) Acute Lymphoblastic Leukemia (ALL) (ASH 2023)
A similar pattern was also observed when olverembatinib was combined with doxorubicin. ConclusionsOlverembatinib, a novel, third-generation TKI, in combination with chemotherapeutic agents vincristine or doxorubicin decreased MCL-1, BCL-2, and BCL-xL and increased BAX and PUMA in a dose-dependent manner, the combinations have demonstrated synergistic antitumor effects by enhancing apoptosis and antiproliferation in Ph⁺ ALL cells, which may provide an alternative approach for treatment of patients with Ph⁺ ALL.
PARP Biomarker • IO biomarker
|
BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1) • CASP3 (Caspase 3)
|
ABL1 T315I
|
doxorubicin hydrochloride • vincristine • Nailike (olverembatinib)
6ms
HQP1351CU101: Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL (clinicaltrials.gov)
P1, N=62, Recruiting, Ascentage Pharma Group Inc. | Trial primary completion date: Jan 2023 --> Jan 2024
Trial primary completion date
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
ABL1 T315I
|
Blincyto (blinatumomab) • Nailike (olverembatinib)
6ms
Long-Term Follow-Up in Patients With Chronic Myeloid Leukemia Treated With Ponatinib in a Real-World Cohort: Safety and Efficacy Analysis. (PubMed, Clin Lymphoma Myeloma Leuk)
CV toxicity was consistent with clinical trials and other real-world registries. Older age, hypercholesterolemia and a SCORE risk >2% were significantly associated with higher risk of AOEs. Controlling CV risk factors and reducing doses at optimal time points may help to optimize ponatinib use in daily practice.
Journal • Real-world evidence • Real-world
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
ABL1 T315I
|
imatinib • Iclusig (ponatinib)
6ms
REAL-WORLD EFFICACY PROFILE OF ASCIMINIB IN AN ITALIAN, MULTI-RESISTANT CHRONIC-PHASE CHRONIC MYELOID LEUKEMIA (CML-CP) PATIENT POPULATION (SIE 2023)
The recent update of the ASCEMBL study demonstrated a superior efficacy with a good tolerability of Asc compared to bosutinib in chronic phase chronic myeloid leukemia (CP-CML) patients (pts) intolerant or refractory to ≥2 TKIs (Rea et al., 2022) Here we present the real-world clinical outcomes of 77 3rd + line Italian CP-CMLpts who received Asc through a Managed Access Program (MAP) approved by Novartis in 41 Italian institutions...Forty-three pts (55.8%) had a prior exposure to ponatinib and 38 of them (88.4%) had ponatinib as last TKI before switching to Asc...In this heavily pre-treated population of CML pts most of whom with a high comorbidity burden, Asc demonstrated fast and sustained responses. Collectively, these results continue to confirm that Asc has a promising role as standard of care in pts with CP-CML treated with ≥2 prior TKI.
Clinical • Real-world evidence • Real-world effectiveness • Real-world
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I
|
Iclusig (ponatinib) • Bosulif (bosutinib) • Scemblix (asciminib)
7ms
The Real-World Outcomes of Ponatinib in 724 Patients with CML and Ph+ ALL : A Post-Marketing Surveillance Study with a Special Interest in Arterial Occlusive Events in Japan (ASH 2023)
Furthermore, regarding AOE, no expression levels exceeding the results of the clinical trial were confirmed. However, patients with advanced age and who have predisposing factors for AOEs should be closely monitored for possible adverse vascular events.
Clinical • P4 data • Real-world evidence • Real-world
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
BCR-ABL1 T315I • ABL1 T315I
|
Iclusig (ponatinib)
7ms
Real-World Effectiveness of Asciminib in Patients with Chronic Myeloid Leukemia (CML) Harboring the T315I Mutation: A Global Chart Review Study of Patients Treated in the Asciminib Managed Access Program (MAP) (ASH 2023)
Background: In patients (pts) with CML, the BCR::ABL1 T315I gatekeeper mutation confers treatment resistance to all approved ATP-competitive tyrosine kinase inhibitors (TKIs) except ponatinib and olverembatinib; thus pts harboring this mutation have limited treatment options. Asciminib demonstrated effectiveness in pts with CML and the T315I mutation in routine medical practice, including ponatinib pre-treated pts, a population with limited available treatment options. Effectiveness estimates were consistent with those observed in clinical trials. Although the number of pts was small, this global study reports on one of the largest cohorts of pts with CML and the T315I mutation.
Clinical • Review • Real-world evidence • Real-world effectiveness • Real-world
|
ABL1 (ABL proto-oncogene 1)
|
BCR-ABL1 T315I • ABL1 T315I
|
Iclusig (ponatinib) • Scemblix (asciminib) • Nailike (olverembatinib)
7ms
Olverembatinib(HQP1351)-Based Therapy in Adults with Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Advanced Chronic Myeloid Leukemia: Results of the Real-Life Study (ASH 2023)
17 (30.4%) patients were pretreated with third-generation TKI (ponatinib). As of the data cutoff date, 37 (66.1%) patients continued on treatment and 19(33.9%) discontinued because of disease progression, intolerance, loss to follow-up or death. Conclusion Olverembatinib-based therapy showed strong efficacy and tolerable toxicity in advanced Ph+ leukemia.
Clinical • IO biomarker • Metastases
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
ABL1 T315I • BCR-ABL1 mutation
|
Iclusig (ponatinib) • Nailike (olverembatinib)
7ms
Combination of Olverembatinib and VP Regimen As First-Line Therapy for Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (ASH 2023)
The upfront use of third generation TKI ponatinib has improved the frequency of complete molecular response (CMR) and the overall survival rate to a greater extent...They received three cycles of OVP regimen(for 28 days each cycle :olverembatinib 40mg qod d1-28,Vindesine 4mg d1,8,15,22,Prednisone1mg/Kg/d d1-21,0.5mg/kg/dd22-28). Twelve intrathecal injections of cytarabine alternating with methotrexate were designed as central nervous system prophylaxis in the following therapy after the diagnosis...The trial is ongoing. we need more time to observe.
Clinical
|
ABL1 (ABL proto-oncogene 1)
|
ABL1 T315I
|
cytarabine • Iclusig (ponatinib) • methotrexate • Nailike (olverembatinib) • vindesine
7ms
Dynamic Changes in ABL1 Kinase Domain Mutations and Comparative Efficacy of Third-Generation Tyrosine Kinase Inhibitors across Different Stages in Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia Blast Crisis Patients (ASH 2023)
Furthermore, through analyzing patients who received TKI treatment, we observed that 3G TKIs like olverembatinib exhibited advantages in prognosis, including achieving deep molecular response, rapid remission reduction, and decreased relapse probability, for both newly diagnosed and relapsed Ph+ ALL patients...The promising outcomes observed with 3G TKIs suggest their potential as a treatment option for both newly diagnosed and relapsed Ph+ ALL patients, offering advantages in terms of molecular response depth, rapid remission, and reduced relapse risk. Further investigations are warranted to explore the clinical significance of unreported ABL1 KD mutations and validate the effectiveness of 3G TKIs against them.
Clinical
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
ABL1 T315I • BCR-ABL1 mutation
|
Nailike (olverembatinib)
7ms
LONG-TERM Results of the Frontline Dasatinib/Blinatumomabprotocol (D-ALBA, GIMEMA LAL2116) for Adult Ph+ Acutelymphoblastic Leukemia (ASH 2023)
These results pave the way for a new era in the treatment of adult Ph+ ALL patients. Vignetti et al, Blood 2007 Foà et al, Blood 2011 Chiaretti et al, Haematologica 2016 Chiaretti et al, Haematologica 2021 Martinelli et al, Blood Advances 2022 Foà et al, N Engl J Med 2020 Foà & Chiaretti, N Engl J Med 2022
Clinical • IO biomarker
|
ABL1 (ABL proto-oncogene 1) • IKZF1 (IKAROS Family Zinc Finger 1)
|
ABL1 T315I • IKZF1 deletion
|
dasatinib • Blincyto (blinatumomab)
7ms
Asciminib (ASC) in Combination with Imatinib (IMA), Nilotinib (NIL), or Dasatinib (DAS) May be a Potential Treatment (Tx) Option in Patients (Pts) with Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase (Ph+ CML-CP/AP): Final Results from the Asciminib Phase 1 Study (ASH 2023)
INTRODUCTION: ATP-competitive tyrosine kinase inhibitors (TKIs) have extended the life expectancy of pts with CML. ASC in combination with ATP-competitive TKIs, while associated with a higher AE burden vs ASC monotherapy, demonstrated rapid efficacy in the enrolled pt population. The MTD for ASC + IMA was reached at ASC 60 mg QD + IMA 400 mg QD (Table); the MTD for ASC + NIL or DAS was not reached. ASC 40 or 60 mg QD + IMA 400 mg QD, ASC 40 mg BID + NIL 300 mg BID, and ASC 80 mg QD + DAS 100 mg QD were recommended doses for expansion.
Clinical • P1 data • Combination therapy
|
ABL1 T315I
|
dasatinib • imatinib • Tasigna (nilotinib) • Scemblix (asciminib) • denifanstat (TVB-2640) • TVB-3567
7ms
Olverembatinib (HQP1351) Demonstrates Efficacy Vs. Best Available Therapy (BAT) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant Chronic Myeloid Leukemia Chronic-Phase (CML-CP) in a Registrational Randomized Phase 2 Study (ASH 2023)
Introduction This was a multicenter, randomized, registrational phase 2 study to assess the efficacy and safety of olverembatinib compared with BAT in pts with CML-CP who were resistant and/or intolerant to 3 TKIs (imatinib [I], dasatinib [D], nilotinib [N]) in China...Pts were randomized 2:1 to investigational olverembatinib (40 mg QOD) or the BAT arm, which could be one of the following per investigator choice: TKIs (I, D, or N), interferon (IFN), hydroxyurea (HU), and homoharringtonine (HHT)...Olverembatinib was observed to be better tolerated and more effective than BAT in treating these pts. Internal study (CT.gov) numbers: HQP1351CC203 (NCT04126681).
Clinical • P2 data
|
ABL1 (ABL proto-oncogene 1)
|
BCR-ABL1 T315I • ABL1 T315I
|
dasatinib • imatinib • Tasigna (nilotinib) • Nailike (olverembatinib) • Synribo (omacetaxine mepesuccinate) • hydroxyurea
7ms
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.
Preclinical
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
|
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
|
Iclusig (ponatinib) • Scemblix (asciminib) • TGRX-678
7ms
Impact of Mutations in Blood Cancer–Related Genes on Clinical Outcomes in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Tyrosine Kinase Inhibitors (TKIs) in the Ascembl Trial (ASH 2023)
With >2 years of follow-up in the phase 3 ASCEMBL study, asciminib (ASC) has continued to demonstrate superior efficacy vs bosutinib (BOS) in pts with CML-CP after ≥2 prior TKIs, and analysis of cancer gene somatic mutations in this population has the potential to reveal additional insights into pts' response to study treatments or characteristics of the disease in later lines of therapy... Adults with CML-CP previously treated with ≥2 TKIs with intolerance of their last TKI or lack of efficacy per 2013 European LeukemiaNet recommendations and without BCR::ABL1 T315I or V299L mutations were randomized 2:1 to ASC 40 mg twice daily or BOS 500 mg once daily... ASXL1 mutations are most frequently detected at CML diagnosis and were enriched at BL in this study of pts with CML-CP previously treated with ≥2 TKIs, which is consistent with a role in TKI resistance. RUNX1 and IKZF1 mutations, which are associated with progression to accelerated or blast phase in CML, were very rare in this pt population, supporting their role in CML disease progression. The high frequency of co-occurrence of BCR::ABL1 mutations and blood cancer gene mutations in CML-CP is an important finding since cancer gene mutations could modify response to TKIs in individual pts.
Clinical • Clinical data
|
ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • IKZF1 (IKAROS Family Zinc Finger 1)
|
BCR-ABL1 T315I • RUNX1 mutation • ASXL1 mutation • MET mutation • ABL1 T315I • IKZF1 deletion • IKZF1 mutation • ABL1 deletion
|
Bosulif (bosutinib) • Scemblix (asciminib) • denifanstat (TVB-2640)
7ms
The Updated Results of Asciminib Managed-Access Program (MAP) in Patients with Chronic Myeloid Leukemia in Russia (ASH 2023)
Background: Therapy choice in chronic myeloid leukemia (CML) patients (pts) with ≥2 lines of tyrosine kinase inhibitors (TKIs) failure or in pts with T315I mutation is a relevant problem. ASC shows effectiveness and good safety profile in pts after prior failure to TKIs and those with T315I mutation. The CIF of any response was higher in ponatinib-naive pts at any dose. Different mutational subclones evolution was observed, including emergence of myristoyl-site mutation in 1 pt.
Clinical
|
ABL1 (ABL proto-oncogene 1)
|
BCR-ABL1 T315I • ABL1 T315I
|
Iclusig (ponatinib) • Scemblix (asciminib)
7ms
Update of Olverembatinib (HQP1351) Overcoming Ponatinib and/or Asciminib Resistance in Patients (Pts) with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) (ASH 2023)
In the combination cohort, pts with Ph+ B-cell precursor (BCP) ALL or lymphoid CML-BP (CML-LBP) resistant to at least 1 TKI were enrolled and received olverembatinib (30 or 40 mg) QOD in combination with blinatumomab. Internal study identifier: HQP1351-CU101. Clinicaltrials.gov identifier: NCT04260022.
Clinical
|
ABL1 (ABL proto-oncogene 1)
|
HER-2 mutation • ABL1 T315I
|
Iclusig (ponatinib) • Blincyto (blinatumomab) • Scemblix (asciminib) • Nailike (olverembatinib)