Scemblix (asciminib) / Novartis - LARVOL DELTA

Luskin MR, Murakami MA, Keating J, et al. Asciminib plus dasatinib and prednisone for Philadelphia chromosome-positive acute leukemia. Blood. 2025;145(6):577-589. (PubMed, Blood) - No abstract available

Journal • Hematological Malignancies • Leukemia • Oncology

Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL. (PubMed, Blood Adv) - P3 | "These long-term results further solidify asciminib as the therapy of choice for patients with CML-CP previously treated with ≥2 prior TKIs. This trial was registered at ClinicalTrials.gov as NCT03106779."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

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

New pediatric formulation of asciminib in children with chronic myeloid leukemia in chronic phase: Second interim analysis of pharmacokinetics and safety from the ASC4Kids study. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT04925479 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Efficacy and safety of asciminib (ASC) in patients (pts) with chronic-phase chronic myeloid leukemia (CML-CP) after 1 tyrosine kinase inhibitor (TKI): Interim analysis (IA) of the phase 2 ASC2ESCALATE trial. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05384587 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P2 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

A phase I study of asciminib in combination with dasatinib, prednisone, and blinatumomab for Ph-positive acute leukemia in adults. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03595917 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • P1 data • Hematological Malignancies • Leukemia • Oncology

Primary endpoint results of the phase 3b ASC4START trial of asciminib (ASC) vs nilotinib (NIL) in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP): Time to treatment discontinuation due to adverse events (TTDAE). (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT05456191 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Adverse events • P3 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Successful treatment of myeloid blast phase chronic myelogenous leukemia with the JAK2 V617 F mutation by combination therapy with asciminib and ropeginterferon alfa-2b in an elderly patient. (PubMed, Int J Hematol) - "Here, we report a case of successful combination therapy with asciminib and ropegIFNα2b in a patient with CML-myeloid BP who had a long history of PV with JAK2 V617F refractory to induction chemotherapy with several TKIs. The combination of asciminib and ropegIFNα2b is a promising new treatment option for these patients."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Polycythemia Vera • Transplantation • ABL1 • IFNA1 • JAK2

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

Enhanced plasma and brain concentrations and medulloblastoma cytotoxicity of asciminib and nilotinib by P-glycoprotein inhibition with tariquidar. (PubMed, Anticancer Drugs) - "Tariquidar prolonged the plasma half-life of asciminib from 2.21 to 10.49 h and nilotinib from 7.63 to 14.64 h. P-glycoprotein inhibition increased the brain concentrations, AUC, and half-life of asciminib and nilotinib and increased cytotoxicity in medulloblastoma cells."

Journal • Brain Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • ABCB1 • ABL1 • ABL2

Which Is the Best Tyrosine Kinase Inhibitor for Newly Diagnosed Chronic Myelogenous Leukemia? (PubMed, Am Soc Clin Oncol Educ Book) - "Currently, five tyrosine kinase inhibitors (TKIs-imatinib, dasatinib, nilotinib, bosutinib, and asciminib) are available for frontline therapy, but no single TKI is optimal for all patients. While the overall treatment failure rate was lower with asciminib, the rate of BCR::ABL1 mutations that emerged with asciminib appeared to be higher. The risk of emergent mutations appears to be highly associated with the presence of ASXL1 mutations in the CML cells at diagnosis, but more work is needed to understand the implications of this finding."

Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1

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

Development and application of a mechanistic pharmacokinetic pharmacodynamic (PKPD) model to predict anti-chronic myeloid leukemia (CML) effects of tyrosine kinase inhibitors (AACR 2025) - "Although tyrosine kinase inhibitors (TKIs) for BCR::ABL1 like imatinib, dasatinib, nilotinib, bosutinib, asciminib and ponatinib are available for CML treatment, novel treatments are needed for CML that is resistant or patients who are intolerant to available therapies. This generalizable PKPD model, using available PK and in vitro potency data, was developed and accurately predicted outcomes of five approved BCR::ABL1 TKIs in patients with newly-diagnosed CML, suggesting the mechanistic PKPD model may be used to predict efficacy for novel TKIs."

PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CRKL • STAT5 • STAT5AWqe

ASC4INDIA: Clinical Study of Asciminib in Previously Treated Indian Patients With Ph+ CML-CP Without T315I Mutation and in Patients With Ph+ CML-CP With T315I Mutation (clinicaltrials.gov) - P4 | N=85 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Olverembatinib in chronic myeloid leukemia-Review of historical development, current status, and future research. (PubMed, Cancer) - P3 | "In clinical trials, olverembatinib exerted potent antileukemic effects in heavily pretreated patients with CML, including those with ponatinib or asciminib resistance or intolerance, and was well tolerated. Future studies include the phase 3 registrational POLARIS-1 (NCT06051409; in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia), POLARIS-2 (NCT06423911; in patients with CML with or without the T315I mutation), and POLARIS-3 (NCT06640361; in patients with succinate dehydrogenase-deficient gastrointestinal stromal tumors) clinical trials."

Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Hematological Malignancies • Leukemia • Oncology • Sarcoma • Solid Tumor • ABL1

Synergistic effect of asciminib with reduced doses of ponatinib in human Ph + myeloid leukemia with the T315M mutation. (PubMed, Int J Hematol) - "Notably, asciminib exhibited a stronger synergistic effect with reduced doses of ponatinib in the T315M-acquired sublines of two myeloid cell lines, but not in the lymphoid cell line. This indicates that the combination of ponatinib and asciminib may have a clinical utility in human Ph + myeloid leukemia."

Journal • Hematological Malignancies • Leukemia • Oncology • ABL1

Cardiac arrhythmias of BCR-ABL inhibitors with or without triazole antifungal agents: A real-world pharmacovigilance study based on the food and drug administration adverse event reporting system database. (PubMed, SAGE Open Med) - "The reporting odds ratios and their 95% confidence intervals for BCR-ABL inhibitor monotherapy, asciminib, nilotinib, and ponatinib were 1.31 (1.27-1.36), 2.11 (1.45-3.06), 2.66 (2.53-2.80), and 1.18 (1.05-1.33), respectively. Dasatinib plus triazole antifungal agents (reporting odds ratio: 2.98, 95% CI: 1.93-4.60) and ponatinib plus triazole antifungal agents (reporting odds ratio: 1.53, 95% CI: 1.08-2.16) were associated with a higher disproportionality of cardiac arrhythmias than BCR-ABL inhibitor monotherapy. The median time-to-onset was longer with monotherapy than with BCR-ABL inhibitors plus triazole antifungal agents (2.63 vs. 0.34 months, p < 0.001), both indicating an early failure type. BCR-ABL inhibitors plus triazole antifungal agents increase the risk of cardiac arrhythmia, particularly in the early stages of treatment, with the risk decreasing over time."

Adverse events • Journal • Real-world evidence • Cardiovascular • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • ABL1 • BCR

ALLOGENEIC TRANSPLANTATION IN A PATIENT WITH REFRACTORY CHRONIC MYELOID LEUKEMIA (EBMT 2025) - "The F359V mutation in the ABL1 gene was identified by Next-Generation Sequencing in November 2022, a mutation affecting the catalytic domain and conferring moderate resistance to Imatinib and Nilotinib.Second-line treatment with Ponatinib was initiated in chronic phase in November 2022 but did not result in molecular response.In April 2023, the patient was diagnosed with lymphoid blastic crisis. Induction therapy was started using the LAL Ph 2008 protocol from the PETHEMA group, with Ponatinib substituted by Dasatinib due to bradycardia associated with Ponatinib...During the second consolidation cycle, Bosutinib was introduced with good tolerance... An allo-HSCT from an HLA-matched sibling was performed in August 2023, conditioning with TBF regimen (Thiothepa, Busulfan, and Fludarabine) and Cyclosporine and Methotrexate in a short-course regimen as prophylaxis for graft-versus-host disease (GVHD)...Donor lymphocyte infusion (DLI) was initiated.After two DLIs, the patient..."

Clinical • Bone Marrow Transplantation • Cardiovascular • Chronic Myeloid Leukemia • Endocrine Disorders • Fatigue • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Leukemia • Musculoskeletal Pain • Oncology • Pain • Transplantation • ABL1

PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto | Trial completion date: Sep 2031 ➔ Jun 2032 | Initiation date: Sep 2024 ➔ Jun 2025 | Trial primary completion date: Sep 2028 ➔ Jun 2029

Trial completion date • Trial initiation date • Trial primary completion date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Asciminib in combination with imatinib, nilotinib, or dasatinib in patients with chronic myeloid leukemia in chronic or accelerated phase: phase 1 study final results. (PubMed, Leukemia) - "Based on these safety, tolerability, and preliminary efficacy results, asciminib 40 mg twice daily (BID) plus nilotinib 300 mg BID, asciminib 40 or 60 mg once daily (QD) plus imatinib 400 mg QD, and asciminib 80 mg QD plus dasatinib 100 mg QD were identified as recommended doses for expansion. The maximum tolerated dose was reached at asciminib 60 mg QD plus imatinib 400 mg QD and was not reached with asciminib plus nilotinib or dasatinib."

Journal • P1 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

A new chapter in CML treatment: the promise of asciminib. (PubMed, Ann Med Surg (Lond)) - "Current research highlights its potential use in pediatric cases and in combination therapies for other leukemia types. Asciminib represents a significant advancement in CML treatment, paving the way for more targeted and tolerable cancer therapies."

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

Asciminib monotherapy in patients with chronic myeloid leukemia in chronic phase without BCR::ABL1T315I treated with at least 2 prior TKIs: Phase 1 final results. (PubMed, Leukemia) - P1 | "The recommended dose for expansion was determined at 40 mg BID. With up to 8.4 years of treatment, asciminib continued to demonstrate long-term safety and efficacy in this population."

Journal • Monotherapy • P1 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Asciminib monotherapy in patients with chronic myeloid leukemia in chronic phase without BCR::ABL1T315I treated with at least 2 prior TKIs: Phase 1 final results (Nature, Leukemia) - P1 | N=326 | NCT02081378 | Sponsor: Novartis Pharmaceuticals | "Median exposure duration was 5.9 (range, 0–8.4) years; 60.9% of patients continued receiving asciminib through post-trial access. Grade ≥3 adverse events (AEs) occurred in 88 patients (76.5%). AEs led to treatment discontinuation, dose adjustment/interruption, or additional therapy in 15 (13.0%), 74 (64.3%), and 106 (92.2%) patients, respectively. Most first-ever AEs, particularly hematologic AEs, presented within the first year and no new safety signals emerged. Of 56 patients who achieved major molecular response, 50 maintained the response by cutoff; the Kaplan-Meier-estimated probability of maintaining this response for ≥432 weeks ( ≈ 8.3 years) was 88% (95% confidence interval, 78.2–97.0%). The recommended dose for expansion was determined at 40 mg BID."

P1 data • Chronic Myeloid Leukemia

Asciminib monotherapy in patients with chronic myeloid leukemia in chronic phase without BCR::ABL1T315I treated with at least 2 prior TKIs: Phase 1 final results (Nature, Leukemia) - P1 | N=326 | NCT02081378 | Sponsor: Novartis Pharmaceuticals | "Median exposure duration was 5.9 (range, 0–8.4) years; 60.9% of patients continued receiving asciminib through post-trial access. Grade ≥3 adverse events (AEs) occurred in 88 patients (76.5%). AEs led to treatment discontinuation, dose adjustment/interruption, or additional therapy in 15 (13.0%), 74 (64.3%), and 106 (92.2%) patients, respectively. Most first-ever AEs, particularly hematologic AEs, presented within the first year and no new safety signals emerged. Of 56 patients who achieved major molecular response, 50 maintained the response by cutoff; the Kaplan-Meier-estimated probability of maintaining this response for ≥432 weeks ( ≈ 8.3 years) was 88% (95% confidence interval, 78.2–97.0%). The recommended dose for expansion was determined at 40 mg BID."

P1 data • Chronic Myeloid Leukemia