Scemblix (asciminib) / Novartis - LARVOL DELTA

FIRST-IN-HUMAN STUDY OF ASCIMINIB (ASC) MONOTHERAPY IN ADULTS WITH RELAPSED/REFRACTORY (R/R) PHILADELPHIA-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (PH+ ALL) (EHA 2025) - P1, P2 | "Pts were heavily pretreated: 89.3% (n=25) had ≥2 prior TKIs, 53.6% (n=15) had prior ponatinib treatment, and 46.4% (n=13) had relapse post transplant. In the current analysis, ASC monotherapy in heavily pretreated pts with Ph+ ALL demonstrated antileukemic activity and was well tolerated, with favorable safety, consistent with parallel studies of ASC in pts with CML. Additional phase 1 cohorts showed that dual treatment with ASC and dasatinib is safe for pts with Ph+ ALL. Ongoing trials are exploring the combination of ASC and blinatumomab (NCT06308588) and ASC with dasatinib, blinatumomab, and steroids (NCT03595917)."

Clinical • Monotherapy • P1 data • Acute Lymphocytic Leukemia • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto | Not yet recruiting ➔ Recruiting

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

Asciminib as Maintenance Treatment After Cellular Therapies for Adults With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P1 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Asciminib With or Without Sildenafil for Brain Tumors (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P1 trial • Brain Cancer • Solid Tumor • ABL2 • CRKL

ASC4KIDS: Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=44 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Jul 2025 ➔ Jun 2026

Trial primary completion date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • ABL1 • BCR

ASCIMINIB AS INITIAL THERAPY WITH ADDITION OF LOWER DOSE TYROSINE KINASE INHIBITORS FOR PATIENTS WITH CHRONIC MYELOID LEUKEMIA WHO DO NOT ACHIEVE OPTIMAL RESPONSE OR A DEEP MOLECULAR REMISSION (ALERT CML): A STUDY FROM THE H JEAN KHOURY CURE CML CONSORTIUM (HJKC3) (EHA 2025) - P2 | "Patients not achieving MR4.5 after 24 months of single agent asciminib will be offered the addition of low dose TKI (imatinib 300 mg, dasatinib 50 mg, or nilotinib 300 mg daily) with the goal to attain MR4.5. In the frontline setting, asciminib monotherapy led to rapid early and subsequent deep responses in pts with CML-CP with a favorable safety profile."

Clinical • Anemia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Dermatology • Fatigue • Hypertension • Insomnia • Musculoskeletal Pain • Neutropenia • Pain • Sleep Disorder • Thrombocytopenia • ABL1

Distinct endothelial cell toxicities mediate thrombotic risk of BCR-ABL tyrosine kinase inhibitors (ISTH 2025) - "However, when the HCAECs were treated with dasatinib or ponatinib, platelet adhesion increased over 5 fold while imatinib, nilotinib, and asciminib had no effect. BCR-ABL-TKIs had no impact on EC expression of thrombomodulin while nilotinib alone increased vWF levels. Table or Figure Upload"

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

ASCIMINIB (ASC) SHOWS SUPERIOR TOLERABILITY VS NILOTINIB (NIL) IN NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP): PRIMARY ENDPOINT RESULTS OF THE PHASE (PH) 3B ASC4START TRIAL (EHA 2025) - P3 | "ASC4START met the primary endpoint in this interim analysis with ASC showing superior tolerability vs NIL based on TTDAE. The study is ongoing, with analyses planned for longer-term tolerability, quality of life, and efficacy. Combined with ASC4FIRST data, results suggest ASC may be a preferred therapy for newly diagnosed CML-CP, enabling more pts to reach tx goals without requiring a tx switch"

Cardiovascular • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Musculoskeletal Pain • Oncology • Pain • Pancreatitis • Thrombocytopenia

ASSESSMENT OF TRANSITIONING FROM HIGH-POTENCY TO LOW-POTENCY INHIBITORS IN CHRONIC MYELOID LEUKEMIA (CML) PATIENTS: THE DOWNGRADING-IMPACT (D-IMPACT) PROJECT, A CML CAMPUS STUDY (EHA 2025) - "TKIs before downgrading: Nilotinib (NIL) (n=73; 46%), Dasatinib (DAS) (n=60; 38%), Ponatinib (n=17; 11%), Bosutinib (BOS) (n=6; 4%), Asciminib (n=1; 1%)...The TKIs used for downgrading were imatinib (IMA) 106 (67.5%), Bosutinib 40 (25.5%), Nilotinib 4 (2.5%), Dasatinib 1(0.6%), Asciminib 5 (3.3%), Interferon 1 (0.6%) (Fig1A)... This exploratory study shows that a downgrading approach can be strategic and safely considered in CML patients, especially for long-term treatment maintaining therapeutic efficacy without adverse clinical outcomes."

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

Treatment-Free Remission in Chronic Myeloid Leukemia: Revisiting the "W" Questions. (PubMed, Eur J Haematol) - "Chronic myeloid leukemia (CML) has undergone a transformation from a fatal disease to a chronic, manageable condition with the advent of tyrosine kinase inhibitors (TKIs), particularly imatinib...Third-generation TKIs like ponatinib and novel agents such as asciminib and olverembatinib offer promising therapeutic alternatives, particularly for patients with the T315I mutation...This review highlights the progress made in CML treatment, emphasizes the need for precision medicine to personalize TFR strategies, and stresses the importance of answering the fundamental "W" questions to advance the field. Future research must focus on refining predictive models, exploring new therapeutic options, and expanding access to treatments to ensure equitable benefits for all CML patients globally."

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

ASCIMINIB AFTER ONE PRIOR TYROSINE KINASE INHIBITOR IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA – A PHYSICIAN PANEL-BASED CHART REVIEW STUDY IN THE UNITED STATES (EHA 2025) - "Imatinib (49.8%), dasatinib (34.5%), nilotinib (10.6%), and bosutinib (5.1%) were received as first TKI. In this first real-world study among patients with CML-CP treated with asciminib after one prior TKI, most patients remained on treatment and achieved or maintained MMR, suggesting that asciminib was well tolerated and effective, consistent with earlier line trials. Findings were consistent across subgroups, indicating that asciminib is an effective option for all patients, including those intolerant or resistant to their first TKI."

Clinical • Review • Chronic Myeloid Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pain • ABL1

ASC4REAL: HARNESSING AI TO REVEAL REAL-WORLD INSIGHTS ON THE EFFECTIVENESS OF ASCIMINIB IN PRE- AND POST-PONATINIB TREATED CML PATIENTS (EHA 2025) - "Asciminib demonstrated a trend towards greater effectiveness in non-PPT CML patients compared to PPT patients, showing higher rates of MR2, MMR, and DMR. Limited responses were observed in PPT patients, particularly those who were refractory to ponatinib, while asciminib appears to maintain responses in patients who discontinued ponatinib due to intolerance. These findings highlight the potential of asciminib as an effective treatment option for CML patients after ≥2 prior TKIs, particularly those who have not demonstrated resistance to ponatinib treatment."

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

REAL-WORLD OUTCOMES OF ASCIMINIB IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA RESISTANT OR INTOLERANT TO TYROSINE KINASE INHIBITORS: A MULTICENTRE CHART REVIEW STUDY IN THE UK (EHA 2025) - "In our cohort, the majority switched to asciminib due to intolerances to previous TKIs. Asciminib demonstrated efficacy in maintaining MMR and DMR as well as deepening responses. At last follow-up, 76.9% of patients remain on asciminib with only 7.7% discontinuing treatment due to intolerances, highlighting its tolerability."

Clinical • Real-world • Real-world evidence • Review • Cardiovascular • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myocardial Infarction • Oncology • Thrombocytopenia • ABL1 • ASXL1 • CSF3R • DNMT3A

INTERIM ANALYSIS (IA) RESULTS FROM ASC2ESCALATE SUPPORT ASCIMINIB (ASC) AS A TREATMENT (TX) OPTION IN CHRONIC-PHASE CHRONIC MYELOID LEUKEMIA (CML-CP) AFTER 1 TYROSINE KINASE INHIBITOR (TKI) (EHA 2025) - P2 | "Pts had received prior dasatinib (44.6%), imatinib (42.6%), nilotinib (9.9%), or bosutinib (5.0%) for ≥12 mo (66.3%), ≥6 to <12 mo (15.8%), or <6 mo (17.8%). In the first prospective trial of 2L ASC in CML-CP, ASC provided high wk 24 molecular response rates and safety and tolerability consistent with previously established 1L and 3L+ ASC data. No new or worsening safety signals arose, and AEs led to discontinuation in <5% of pts. These IA results support ASC as a 2L tx option in CML-CP."

Cardiovascular • Chronic Myeloid Leukemia • Dyspepsia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Movement Disorders • Neutropenia • Oncology • Pain • Thrombocytopenia

ASCIMINIB AS SECOND-LINE THERAPY FOR CHRONIC MYELOID LEUKEMIA: CANADIAN AND INTERNATIONAL REAL-WORLD EXPERIENCE (EHA 2025) - "Three patients had a history of cardiovascular disease.The first-line TKIs used were: dasatinib in 8 patients (53%), nilotinib in 6 patients (40%), and imatinib in 1 patient (7%). ASC as a second-line TKI shows encouraging results. Further analysis of larger cohorts is required."

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

IMPROVED PATIENT-REPORTED OUTCOMES (PROS) WITH ASCIMINIB (ASC) VS INVESTIGATOR-SELECTED TYROSINE KINASE INHIBITORS (IS-TKIS) IN NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA (CML): ASC4FIRST WK 48 ANALYSIS (EHA 2025) - P3 | "PRO-CTCAE items were fatigue, vomiting, nausea, loose/watery stools, headache, arm/leg swelling, rash, itchy skin, and aching muscles.Adults with newly diagnosed CML-CP were randomized 1:1 to receive ASC or an IS-TKI and stratified by ELTS risk category and prerandomization selected TKI (imatinib/second-generation TKI). In ASC4FIRST, ASC was associated with improvements in HRQOL, cognitive and social functioning, symptom burden, and impact on daily life and satisfaction with care and information compared with IS-TKIs at wk 48. PROs, along with the superior efficacy and remarkable safety profile of ASC in ASC4FIRST, continue to support ASC as a tx of choice for newly diagnosed CML-CP."

Clinical • Patient reported outcomes • Chronic Myeloid Leukemia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Oncology • Pain • Pruritus

OVERCOMING ASCIMINIB RESISTANCE IN CHRONIC MYELOID LEUKEMIA WITH IDENTIFICATION OF THERAPEUTIC STRATEGIES TARGETING BCR::ABL1 MUTATIONS (EHA 2025) - "The T315I and Y139D mutations confer substantial asciminib resistance. While ponatinib-asciminib co-treatment was effective against certain BCR::ABL1 mutations, it failed in compound-resistant cells. In contrast, bortezomib-panobinostat combination therapy exhibited potent synergy, supporting its potential as an alternative strategy for asciminib-resistant CML."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CASP3 • CASP7

ENABLE: A PHASE 1A/1B STUDY OF ELVN-001, A SELECTIVE ACTIVE SITE INHIBITOR OF BCR::ABL1, IN PATIENTS WITH PREVIOUSLY TREATED CML (EHA 2025) - P1 | "The majority of patients (66%) had received ≥3 prior TKIs, including ponatinib (45%) andasciminib (57%). ELVN-001 demonstrated favorable safety and tolerability across a wide range of doses, consistent with its selective kinase profile. Despite the heavily pretreated patient population, encouraging preliminary efficacy was observed, including in patients with asciminib-resistant mutations."

Clinical • P1 data • Chronic Myeloid Leukemia • Hematological Disorders • Neutropenia • Pancreatitis • Thrombocytopenia • ABL1

WHAT'S THE PRICE FOR THE BEST? PHARMACOECONOMIC COMPARISON OF ASCIMINIB AND IMATINIB IN FIRST LINE OF CHRONIC MYELOGENOUS LEUKEMIA TREATMENT (EHA 2025) - "Pharmacoeconomic modelling can simulate budget burden and its future dynamics on the group and national level. The results of such modelling can be used in decision making process for the national treatment standards development and budget allowance. There are many limitations of this study due to simulation and stipulation of some important input parameters."

Clinical • HEOR • 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, SAFETY AND GROWTH DATA FROM THE ASC4KIDS STUDY (EHA 2025) - P1/2 | "The PF dose of 1.3 mg/kg BID was well tolerated and showed evidence of efficacy in a larger cohort of children, with no new safety signals. Preliminary data shows ASC did not negatively impact growth. A 2.6 mg/kg QD dose will be assessed in Part 3."

Clinical • PK/PD data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Oncology • Pain • Pediatrics • Respiratory Diseases

ASSESSMENT OF DRUG-DRUG INTERACTION POTENTIAL BETWEEN ASCIMINIB AND ATORVASTATIN IN HEALTHY PARTICIPANTS (EHA 2025) - "When administered with atorvastatin, asciminib (80 mg QD) under steady state conditions resulted in small, not clinically relevant, increases in the exposure of atorvastatin. Multiple doses of asciminib, given alone or concomitantly with atorvastatin, were well tolerated by the healthy participants in this study."

Clinical • Cardiovascular • Chronic Myeloid Leukemia • Dermatology • Dyslipidemia • Hematological Malignancies • Leukemia • Oncology • Pruritus

ASC4OPT STUDY: HIGH EFFICACY AND FAVORABLE TOLERABILITY OF ASCIMINIB ONCE OR TWICE DAILY IN CML PATIENTS WITH SUBOPTIMAL RESPONSE, RESISTANCE OR INTOLERANCE OF 2 OR MORE TYROSINE KINASE INHIBITORS (EHA 2025) - P3 | "Pts were randomized 1:1 to receive ASC 40 mg BID or 80 mg QD. The ASC4OPT findings strengthen those of the ASCEMBL study, supporting ASC as a standard of care for pts with CML-CP pretreated with ≥2 TKIs; the more convenient 80 mg QD regimen may enhance treatment adherence and ultimately improve patient outcomes. Pts who discontinued previous TKIs due to intolerance were able to maintain or deepen responses on ASC regardless of dosing schedule."

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

BCR-ABL1 kinase domain mutations associated with asciminib (EHA 2025) - No abstract available

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

DE-ESCALATION AND TREATMENT-FREE REMISSION IN CHRONIC MYELOID LEUKEMIA PATIENTS RECEIVING SALVAGE THERAPY FOR RESISTANCE, WARNING OR LACK OF DEEP MOLECULAR RESPONSE (EHA 2025) - "Imatinib was the 1st line TKI in all but one pt who received nilotinib...Last TKI prior to discontinuation was a 2nd generation drug (dasatinib, nilotinib or bosutinib) in 88% of pts, a 3rd generation compound (ponatinib) in 7% of pts and the allosteric TKI asciminib in 2% of pts... TKI discontinuation is pts with prior history of resistance, warning or lack of DMR appears feasible and safe in our experience. A larger series is required to draw firm conclusions, but our results pave the way for recommendations in clinical practice. Maintenance of a DMR after therapy de-escalation might identify pts with high probabilities of TFR success."

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

ACHIEVING TREATMENT FREE REMISSION IN CML PATIENTS TREATED WITH BOSUTINIB: DATA FROM THE ITALY-TFR REGISTRY (EHA 2025) - P=N/A, P3 | "While TKI discontinuation has become clinical practice for patients (pts) treated frontline with imatinib, nilotinib and dasatinib who achieve a stable deep molecular response (DMR), data on bosutinib discontinuation are more limited and further studies are needed to assess its potential for treatment free remission (TFR). In fact only a single center study focusing on ponatinib and bosutinib discontinuation is reported, which includes 8 pts who discontinued bosutinib mostly due to toxicity...One patient restarted bosutinib, 1 patient started asciminib, 1 patient nilotinib and 1 patient imatinib... Our preliminary analysis suggests that discontinuing Bosutinib is as safe as discontinuing other TKIs, confirming the single center experience reported in literature. Our patients suspended by clinical decision rather than toxicity. The depth of molecular response was the strongest predictor of successful TFR for the cases already reported in literature."

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