Iclusig (ponatinib) / Takeda, Otsuka, Incyte - LARVOL DELTA

Treatment of Older Patients With ALL. (PubMed, Am Soc Clin Oncol Educ Book) - "In Ph-negative ALL, the duration and intensity of chemotherapy was reduced, and outcomes improved with the addition of inotuzumab ozogamicin (InO) and blinatumomab into the frontline setting...The combination of blinatumomab and ponatinib induced high rates of complete molecular responses and excellent survival, without reliance on HSCT. A subset of patients with elevated WBC count at diagnosis are at particular risk of CNS and systemic relapse and may require additional strategies such as incorporating one to two cycles of high-dose methotrexate/cytarabine into consolidation, and potentially CAR T cells. In T-cell ALL, adding venetoclax into the frontline setting has improved outcomes. In early T-cell precursor ALL, HSCT is still needed. To further improve outcomes in older patients, novel agents such as subcutaneous blinatumomab, CAR T cells, newer-generation TKIs, and menin inhibitors should be investigated in the frontline setting."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation • ABL1

In Vitro Drug Profiling to Guide Treatment for Relapse/Refractory AML (ASH 2024) - "Significant correlation was observed among drugs of the same classes, for example between inhibitors of PARP (e.g. niraparib-talazoparib, r=0.78, p=1.3e-22), proteasome (e.g. bortezomib-ixazomib, r=0.90, p=4.2e-36), JAK (ruxolitinib-tofacitinib, r=0.91, p=8.3e-35), MEK (cobimetinib-trametinib, p=0.93, p=8.8e-47) and CDK (abemaciclib-palbociclib, p=0.56, p=2.7e-10), confirming that the readout is biologically meaningful. Intriguingly, there were unexpected correlations between specific pairs of drugs of different classes, for instance homoharringtonine (protein translation inhibitor)-abemaciclib (CDK inhibitor) (r=0.65, p=4.3e-17) and between specific gene mutations and drug sensitivity was observed, e.g. sensitivity of CEBPAbZIP mutated samples to PARP inhibitors (p=0.00156), and of AML with inv(16) to MEK inhibitors (p=0.0016)...Drug response to daunorubicin showed good prediction of chemo-resistance in patients who had non-remission after "7+3" (ROC curve AUC..."

Preclinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • ANXA5 • FLT3

NCI-2018-01100: Venetoclax, Ponatinib, and Dexamethasone in Participants With Philadelphia Chromosome or BCR-ABL Positive Relapsed or Refractory Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia (clinicaltrials.gov) - P1/2 | N=9 | Terminated | Sponsor: M.D. Anderson Cancer Center | Completed ➔ Terminated; The study was terminated early due to slow accrual and low level of interest both by the sponsor and by the department

Trial termination • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ABL1 • BCL2 • BCR

Real-World Efficacy Profile of Compassionate Use of Asciminib in an Italian, Multi-Resistant Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Patient Population. (PubMed, Hematol Oncol) - "Patients were heavily pretreated with a median of 3 TKIs (55.8% had prior ponatinib exposure). These results highlight asciminib remarkable tolerability and efficacy in real-world CML-CP patient population, including heavily pretreated patients, those intolerant and resistant to previous TKIs, and presenting several comorbidities. TRAIL REGISTRATION: The identification code for the MAP is CABL001AIT01M."

Journal • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Three cases of drug-induced ponatinib-induced cerebral vascular stenosis and cerebral infarction (JSNE 2025) - No abstract available

Clinical • CNS Disorders

Clarification and overcoming the resistance mechanisms to inotuzumab ozogamicin and ponatinib in B-ALL (AACR 2025) - "The combination of IO and a p-gp inhibitor, PSC-833, decreased the IC50 values of IO by 90% and increased apoptosis...When combined with IO and PARP inhibitors, olaparib and talazoparib, increased the IO sensitivity of resistant cell lines by 50 to 90%...DNA microarray showed that JAK2 expression was upregulated in resistant cell line.[Conclusion] The present study indicated that inhibition of drug efflux and DNA damage repair overcame the resistance to IO in Ph-negative B-ALL. Moreover, JAK2 might be the therapeutic target to overcome the resistance to ponatinib in Ph-positive B-ALL."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABCB1 • JAK2

Fangzhou Launches Otsuka's Third-Generation Leukemia Drug Ponatinib on its Platform (PRNewswire) - "Fangzhou Inc...announced the availability of Otsuka Pharmaceutical's third-generation tyrosine kinase inhibitor (TKI) Iclusig (ponatinib) through its online platform, providing expanded treatment options for patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)."

Launch • Chronic Myeloid Leukemia • T Acute Lymphoblastic Leukemia

The evolving therapeutic revolution in adult acute lymphoblastic leukemia. (PubMed, Cancer) - "The ongoing therapeutic revolution in ALL is driven by the addition to the treatment arsenal of therapies that target the ABL fusions, like the BCR::ABL1 tyrosine kinase inhibitors, as well as novel agents that target CD19 and CD22: the CD22 antibody-drug conjugate inotuzumab ozogamicin, the bispecific CD3/CD19 T-cell engager antibody blinatumomab, and CD19 chimeric antigen receptor T-cell therapies. These combinations have improved the long-term survival rates in B-cell ALL to 70%, and in Philadelphia chromosome-positive ALL to 80%-90%. The desired goals are to achieve cure rates comparable to those in pediatric ALL and to reduce or eliminate the need for prolonged intensive/maintenance chemotherapy and associated toxicities."

Journal • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • ABL1 • CD22

Patient-reported toxicity symptoms during tyrosine kinase inhibitor treatment in chronic myeloid leukemia: a systematic review and meta-analysis. (PubMed, Support Care Cancer) - "Our findings provide essential information to guide treatment decisions in cases of intolerability. However, there is a clear need for further research with standardized instruments, especially in second and third generation TKI types, including direct comparisons and comparisons adjusted for covariates."

Clinical • Journal • Retrospective data • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Navigating the Diagnosis and Management of Pleural Solitary Fibrous Tumors: A Case Study (ATS 2025) - "With oncology's goal of pursuing palliative and survival benefit, the patient began chemotherapy with Dacarbazine and Doxorubicin. Furthermore, this study demonstrated that Trabectedin combined with either Ponatinib or Dasatinib had synergistic effects, suggesting two potential new treatment strategies for pleural SFT in the future. Further randomized controlled clinical trials and analytical research are needed to identify effective treatments for SFT."

Case study • Clinical • Cough • Fibrosis • Oncology • Pain • Pulmonary Disease • Respiratory Diseases • Sarcoma • Solid Tumor • Spindle Cell Sarcoma

Investigating the efficacy and safety of ponatinib in acute lymphoblastic leukemia: A systematic review. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Efficacy and safety of combination therapy of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: A systematic review and meta-analysis. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Combination therapy • Retrospective data • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

OPTIC: Ponatinib in Participants With Resistant Chronic Phase Chronic Myeloid Leukemia (CP-CML) to Characterize the Efficacy and Safety of a Range of Doses (clinicaltrials.gov) - P2 | N=283 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Trial completion • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Management of Adult Acute Lymphoblastic Leukemia: A Review. (PubMed, JAMA Oncol) - "The novel therapies include using the more potent BCR::ABL1 tyrosine kinase inhibitors (eg, ponatinib, dasatinib) with the bispecific CD3-CD19 T-cell engager antibody blinatumomab in Philadelphia chromosome-positive ALL and combining blinatumomab and/or inotuzumab (CD22 antibody drug conjugate) with standard chemotherapy in B-cell ALL. Investigators have evaluated frontline and later-line regimens with combinations of tyrosine kinase inhibitors and immunotherapies with less or no chemotherapy. Future research will evaluate CD19, CD20, and CD22 multitargeting antibodies and chimeric antigen receptor T-cell therapies, new antibody formulations, and less intensive/shorter regimens."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ABL1 • CD20 • CD22

Drug-induced pancreatitis: a real-world analysis of the FDA Adverse Event Reporting System and network pharmacology. (PubMed, Front Pharmacol) - "Ponatinib (16.48%), tigecycline (14.12%) and valproic acid (13.41%) had higher fatality rates. Potential targets related to pancreatitis were identified in 50 of the 101 drugs. Clinicians providing the 101 drugs for treatment should stay vigilant to detect pancreatitis early."

Adverse events • Journal • Real-world evidence • Pancreatitis • Rare Diseases

Novel tyrosine kinase/MEK inhibitor combinations impair the viability and invasive potential of TNBC cell lines (AACR 2025) - "We identified several cytokines secreted in response to the pan-Raf inhibitor CCT196969, the MEK inhibitor (MEKi) trametinib and the ERK inhibitor (ERKi) ulixertinib such as FGF-basic, FGF-19, MIF and angiogenin. Lastly, the trametinib/ALW-II-41-27 combination revealed a significant reduction in cell migration and invasion compared to trametinib treatment alone. These findings indicate that ponatinib and ALW-II-41-27 combined with MAPKi could be a promising novel therapeutic approach for TNBC."

Preclinical • Oncology • Triple Negative Breast Cancer • ALK • ERBB3 • FGF19 • FGFR1 • FGFR3 • HER-2

Identification and characterization of binding thermodynamics and kinetics of inhibitors targeting FGFR1 via molecular modelling and ligand Gaussian accelerated molecular dynamics simulations. (PubMed, Phys Chem Chem Phys) - "The binding constant was estimated to be 7.4 ± 0.27 nM, which was similar to the type II tyrosine kinase inhibitor ponatinib. Overall, this study highlights the dynamics of FGFR1-ligand interaction while proposing bevantolol and its analogue molecule ANLG-2 as promising drug candidates for FGFR1 therapeutic intervention."

Journal • Oncology • FGFR1

Phase-1 study of vamotinib (PF-114), a 3rd generation BCR::ABL1 tyrosine kinase-inhibitor, in chronic myeloid leukaemia. (PubMed, Ann Hematol) - "2 of 5 subjects failing ponatinib achieved a CHR. Vamotinib dose for further phase-3 study is 300 mg/d."

Journal • P1 data • Chronic Myeloid Leukemia • Dermatology • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Psoriasis • ABL1

Hematologist-Oncologist Preferences for Treating Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) using Tyrosine Kinase Inhibitors in Combination with Chemotherapy: A Discrete Choice Experiment (ISPOR 2025) - "OBJECTIVES: The treatment landscape for newly-diagnosed Ph+ ALL is evolving, with FDA approval of the first TKI (ponatinib) in combination with chemotherapy in 2024... Despite varied relative importance for treatment benefits and risks across the different patient profiles, increasing MRD-negative CR remained the primary consideration for physicians, irrespective of the patient profile."

Combination therapy • Acute Lymphocytic Leukemia • Cardiovascular • Diabetes • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Metabolic Disorders • Oncology

Real-World Patient Characteristics and Treatment Patterns in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia Patients With Long-Term Survivorship (ISPOR 2025) - "Prior to R/R, 66% received "hyper CVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride/adriamycin, dexamethasone, methotrexate, cytarabine) plus (imatinib, ponatinib, dasatinib, rituximab)", 95%/40%/11%/36% received induction/consolidation/allo-SCT as consolidation/maintenance. LTS was prevalent among younger patients achieving MRD who were thus more likely to receive allo-SCT consolidation/maintenance therapy. Limited observations were available for some newer therapeutics, the earlier use of which among poorer-prognostic patients may contribute to LTS."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Comprehensive Analysis of ABL1 Variant Resistance to Multiple Kinase Inhibitors via Prime Editing (ASGCT 2025) - "We then assessed the resistance profiles of these SAAVs against a panel of five TKIs—imatinib, nilotinib, bosutinib, ponatinib, and asciminib—representing all four TKI generations, using CML-relevant K562 cells. The comprehensive resistance landscape generated in this study serves as a valuable resource to refine clinical decision-making and enhance precision medicine strategies for CML patients by providing an evidence-based framework for drug selection based on ABL1 mutation status. Disease Focus of Abstract:Cancer Hematologic"

Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • ABL1

Effect of ponatinib on the metabolism of cariprazine in vitro and in vivo and the underlying mechanism. (PubMed, Toxicol Appl Pharmacol) - "The objective of the present study was to examine the inhibitory impacts of three antitumor drugs (olmutinib, napabucasin and ponatinib) on the metabolism of cariprazine, and the molecular docking of cariprazine and ponatinib in relation to CYP3A4 was also evaluated. Molecular docking studies had demonstrated that both cariprazine and ponatinib could engage in hydrophobic interactions with residue PHE-304 on CYP3A4. Consequently, when ponatinib is employed in conjunction with cariprazine in a clinical setting, it is imperative to assess the efficacy and adverse effects, and adjust the dosage to attain the optimal efficacy."

Journal • Preclinical • CNS Disorders • Mental Retardation • Oncology • Psychiatry • Schizophrenia • CYP3A4

Discovery of Genomic Targets and Therapeutic Candidates for Liver Cancer Using Single-Cell RNA Sequencing and Molecular Docking. (PubMed, Biology (Basel)) - "The proposed candidates include Adozelesin, Tivozanib, NVP-BHG712, Nilotinib, Entrectinib, Irinotecan, Ponatinib, and YM201636. This study provides critical insights into the genomic landscape of liver cancer and identifies promising therapeutic candidates, serving as a valuable resource for advancing liver cancer research and treatment strategies."

Journal • Hepatology • Liver Cancer • Oncology • Solid Tumor

Development of a BCR-ABL degrader overcoming resistance by BCR-ABL1 kinase domain mutations in chronic myeloid leukemia (AACR 2025) - "Additionally, we evaluated the effects of single and combination therapies with TKIs (Asciminib or Ponatinib) using cell proliferation assays in K562 and Ba/F3 BCR-ABL1 mutant cell lines. These preclinical findings suggest the potential for the clinical development of a BCR-ABL1 degrader. Furthermore, UBX-362 demonstrates the ability to overcome resistance in CML patients with BCR-ABL1 mutations and shows promise as a candidate for combination therapy with other BCR-ABL1 inhibitors, providing new therapeutic possibilities for CML patients."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

ELVN-001, a highly selective ATP-competitive ABL1 tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia alone or in combination with asciminib (AACR 2025) - "While the active-site TKI ponatinib is active against T315I, its poor kinome selectivity limits its clinical utility. Finally, ENU mutagenesis screens were conducted in a Ba/F3 BCR-ABL1 line with ELVN-001 and asciminib, alone and in combination. Results of these studies and their impact on the clinical utility of this combination will be discussed."

Combination therapy • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • FLT3 • KDR • KIT