Scemblix (asciminib) / Novartis - LARVOL DELTA

ENABLE: A Phase 1 Study of ELVN-001, a Novel, Selective ATP-Competitive Inhibitor of BCR::ABL1, in Patients With Previously Treated CP-CML (SOHO 2026) - P1 | " Of 141 patients (median age, 58 years), nine had atypical BCR::ABL1 transcripts and 28 had ABL1 kinase mutations (15 with T315I; 12 with asciminib-resistance mutations); 67% received ≥3 prior TKIs (24% with ≥5 TKIs; 61% prior asciminib; 38% prior ponatinib), with 64% discontinuing the prior TKI due to lack of efficacy (according to ELN guidelines). In this updated analysis of ENABLE, ELVN-001 showed favorable safety and tolerability and robust anti-CML activity in heavily pretreated patients. ABL1: ABL proto-oncogene 1, non-receptor tyrosine kinase, ATP: adenosine triphosphate, BCR::ABL1: breakpoint cluster region–Abelson 1, CML: chronic myeloid leukemia, CP: chronic phase, ELN: European LeukemiaNet, MMR: major molecular response, T315I: threonine-to-isoleucine mutation at position 315."

Clinical • P1 data • Chronic Myeloid Leukemia • Oncology • ABL1 • BCR

Integrating Asciminib into the Evolving Treatment Landscape of Chronic Myeloid Leukemia: A Canadian Perspective. (PubMed, J Blood Med) - "We also explore the role of next-generation sequencing in detecting salvageable resistance mutations, the prognostic significance of co-mutations such as ASXL1, and the concept of mutation-guided treatment sequencing. Collectively, these data position asciminib as an established later-line therapy and an emerging frontline option, with the potential to improve long-term treatment sustainability through favorable tolerability and early molecular response kinetics."

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

A Case of Duffy-Null-Associated Neutropenia in a Patient With Chronic Myeloid Leukemia. (PubMed, Case Rep Hematol) - "Subsequently, she began treatment with imatinib (Gleevec) 400 mg daily...After several treatment changes due to adverse effects, she began treatment with asciminib 80 mg daily...Early detection of Duffy-null status can prevent dose reductions in therapy and delayed remission. Particularly with African American patients, a better framework for addressing Duffy-null neutropenia may benefit long-term outcomes in the setting of cancer therapy."

Journal • Chronic Myeloid Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • ABL1 • BCR

Phase II Study Assessing Efficacy and Safety of Asciminib in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase. (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: M.D. Anderson Cancer Center | N=50 ➔ 150

Enrollment change • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Dual-Driver Myeloproliferative Neoplasm: Concurrent p190 BCR::ABL1 CML and JAK2 V617F Mutation: A Case Report and Literature Review. (PubMed, Case Rep Hematol) - "The patient received first-line asciminib and was subsequently transitioned to dasatinib, with the BCR::ABL1/ABL1 ratio declining from 88.5% at diagnosis to 0.79% at most recent assessment. The admixed megakaryocytic atypia superimposed on myeloid hyperplasia reflected the coexistence of two drivers. Comprehensive profiling, including high-sensitivity RT-PCR capable of detecting the p190 isoform and concurrent JAK2 testing, is essential for accurate diagnosis, prognostication, and therapy selection in these rare dual-driver cases."

Journal • Chronic Myeloid Leukemia • Essential Thrombocythemia • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • Thrombocytosis • ABL1 • BCR • JAK2

Asciminib Demonstrates Superior Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia in the ASC4FIRST Trial. (PubMed, Blood) - "The hazard ratio for time to discontinuation of treatment due to AEs for asciminib vs 2G TKIs was 0.46 (95% CI, 0.215%-0.997%). With longer follow-up, asciminib continued to demonstrate a favorable benefit-risk profile over IS-TKIs and imatinib, supporting its potential as a treatment option for newly diagnosed CML-CP."

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

N-Myristoylation: A Central Hub Integrating Tumor Signaling, Metabolism, and Immunity for Precision Therapy. (PubMed, Med Res Rev) - "Antitumor potential of NMT inhibitors (e.g., B-13, Zelenirstat) and allosteric ABL1 inhibitors (asciminib) is evaluated. Addressing these will require combination therapies tailored to specific mutational, metabolic, and immune profiles. In summary, N-myristoylation integrates signaling, metabolism, and immunity, offering a rationale for future precision oncology."

IO biomarker • Journal • Review • Oncology • AMPK

Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI) (ASH 2024) - P2 | "Pts had received prior treatment with imatinib (32.6%), dasatinib (48.8%), nilotinib (16.3%), or bosutinib (2.3%); 76.7% had received their prior TKI for ≥12 mo. These promising results support asciminib as a potential treatment option in these pts. Updated data (data cutoff June 28, 2024) will be presented at the ASH 2024 Annual Meeting."

Clinical • P2 data • Cardiovascular • Chronic Myeloid Leukemia • Cough • Fatigue • Hematological Malignancies • Hypertension • Leukemia • Oncology • Respiratory Diseases

ASCIMINIB (ASC) PROVIDES SUPERIOR EFFICACY AND EXCELLENT SAFETY AND TOLERABILITY VS TYROSINE KINASE INHIBITORS (TKI) IN NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA (CML) IN THE PIVOTAL ASC4FIRST STUDY (EHA 2024) - P3 | "ASC, the first BCR::ABL1 inhibitor to Specifically Target theABL Myristoyl Pocket (STAMP), was intentionally designed to be highly specific and minimize off-target effects.We report primary results from ASC4FIRST (NCT04971226), a randomized ph 3 study of ASC vs all currentstandard-of-care frontline TKIs in pts with newly diagnosed CML.Aims:The two primary objectives were to demonstrate superior major molecular response (MMR) rate at wk 48 withASC vs investigator-selected (IS) TKI and ASC vs IS TKI within the stratum of pts with imatinib (IMA) as theirprerandomization-selected (PRS) TKI (ASCIMA vs IS TKIIMA). Pts received ASC (n=201: ASCIMA, n=101; ASC2G, n=100) or an IS TKI (n=204: IS TKIIMA, n=102; IS TKI2G,n=102 [nilotinib, 48%; dasatinib, 41%; and bosutinib, 11%]). Median follow-up was 16.3 and 15.7 mo with ASCand IS TKIs, respectively. At cutoff (Nov 28, 2023), Tx was ongoing in 86%, 62%, and 75% of pts receiving ASC,IMA, and 2G TKIs, respectively (Figure).MMR..."

Clinical • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

ASC4FIRST WK 144 ANALYSIS: CONTINUED SUPERIOR EFFICACY AND FAVORABLE SAFETY OF ASCIMINIB VS INVESTIGATOR-SELECTED TYROSINE KINASE INHIBITORS IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKEMIA (EHA 2026) - P3 | "2025) analyses, asciminib (ASC) had superior efficacy and improved safety/tolerability vs investigator-selected tyrosine kinase inhibitors (IS-TKIs: imatinib [IMA] and second generation [2G] TKIs), and a better benefit-risk profile vs 2G TKIs...No new BCR::ABL1 mutations emerged with ASC after wk 96; 1 each emerged with IMA and nilotinib...Reused with permission. This abstract was accepted and previously presented at the 2026 ASCO Annual Meeting."

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

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) - P1 | "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 • Combination therapy • P1 data • Chronic Myeloid Leukemia • Fatigue • Hematological Malignancies • Leukemia • Oncology

Sustained Efficacy and Safety with Asciminib (ASC) after Almost 4 Years of Median Follow-up from Ascembl, a Phase 3 Study of ASC Vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): An End of Study Treatment (EOS Tx) Update, Including Results from Switch Population (ASH 2023) - " Adults (aged ≥18 y) with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 ELN recommendations were randomized 2:1 to receive either ASC 40 mg twice daily or BOS 500 mg once daily. With almost 4 y of follow-up in ASCEMBL, ASC continued to show greater efficacy and better safety/tolerability than BOS in pts with CML-CP after ≥2 prior TKIs. The robust safety profile of ASC was sustained through each analysis in ASCEMBL (wk 24, wk 96, and EOS Tx), confirming that pts receiving ASC can maintain a high level of response and continue Tx without experiencing late-emerging AEs. Results in the switch population support the use of ASC early in the Tx paradigm."

Clinical • P3 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Atherothrombotic Adverse Effects of Tyrosine Kinase Inhibitors in Patients With Chronic Myeloid Leukemia (SOHO 2026) - " The patients were receiving imatinib (26 patients; 16%), nilotinib (50 patients; 31%), dasatinib (26 patients; 16%), bosutinib (4 patients; 3%), ponatinib (44 patients; 28%), asciminib (7 patients; 6%), and vamotinib (2 patients; 1%). In patients with CML, ATAEs are associated with initially high CV risk. Nilotinib and ponatinib demonstrated the most unfavorable toxicity profiles. These findings highlight the importance of CV risk assessment before TKI initiation and its dynamic monitoring during treatment."

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

Asciminib (ASC) Add-on to Imatinib (IMA) Demonstrates Sustained High Rates of Ongoing Therapy and Deep Molecular Responses (DMRs) with Prolonged Follow-up in the ASC4MORE Study (ASH 2023) - P2 | "Here, we report results of ASC add-on to IMA vs continued IMA vs switch to nilotinib (NIL) and of pts who crossed over from continued IMA to ASC add-on after 96 wks of Tx in pts not achieving DMR with ≥1 y of IMA as their first TKI (cutoff: 6 Mar 2023)...The top reasons for discontinuation were pt decision (9.5% with ASC 40 mg add-on), adverse events (AEs; 14.3% and 33.3%, with ASC 60 mg add-on and NIL, respectively), and physician decision (66.7% with IMA, all of whom crossed over to ASC 60 mg add-on)... Among pts not achieving DMR after ≥1 y on IMA, more pts achieved MR4.5 with ASC add-on to IMA than with continuing IMA or switching to NIL at wk 96. Pts crossing over from IMA to ASC 60 mg add-on were still able to achieve DMRs. ASC add-on to IMA was well-tolerated, with no new or worsening safety findings compared with those known for ASC alone."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Allosteric kinase inhibition in hematological malignancies: from asciminib to emerging regulatory sites. (PubMed, Biochem Pharmacol) - "This review fills that gap with two contributions: mechanistic evidence that crizotinib engages BCR::ABL1 through a putative dual ATP-site/myristoyl-pocket mechanism, supported by indirect evidence and pending direct structural confirmation; and a hypothesis linking recurrent synonymous mutations in non-receptor tyrosine kinases to transiently structured regulatory regions, as a strategy for identifying latent allosteric sites Asciminib is the proof of concept...In the ASCEMBL trial, it achieved a major molecular response rate of 25.5% at 24 weeks versus 13.2% for bosutinib in heavily pretreated CML, with better tolerability-the first regulatory-site inhibitor approved for a hematological malignancy...Asciminib resistance is already real: A337V and P465S mutations reduce binding, and bypass signaling adds another layer. Each approved allosteric agent-asciminib, trametinib, and ivosidenib-required extensive structural and functional validation before reaching the clinic;..."

Journal • Review • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Oncology • ABL1 • FLT3 • JAK2

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

Safety and Efficacy of Tgrx-678, a Potent BCR::ABL1 allosteric Inhibitor, in Patients with Tyrosine Kinase Inhibitor Resistant and/or Intolerant Chronic Myeloid Leukemia: Updated Results of Phase 1 Study Tgrx-678 -1001 (ASH 2024) - P1, P2 | "Methods : In phase Ia, CML-CP and CML-AP patients who were R/I at least to imatinib, dasatinib and nilotinib were enrolled...Patients were heavily pretreated; 71 (66%) CP and 44 (88%) AP patients had received ≥ 3 prior TKIs; 40 (37%) CP and 30 (60%) AP patients had previously received ponatinib, olverembatinib, asciminib, and/or HS-10382 (a new STAMP inhibitor)...The updated data indicate promising efficacy in both CP and AP patients including those with the T315I mutation and those who failed 3G-TKI or STAMP inhibitors. Ongoing Phase 2 trials in China (NCT NCT06453902) and Phase 1 trials in US (NCT06088888) are further evaluating TGRX-678, underscoring the need for continued assessment."

Clinical • P1 data • Anemia • Chronic Myeloid Leukemia • Diabetes • Dyslipidemia • Hypertriglyceridemia • Leukopenia • Metabolic Disorders • Neutropenia • Thrombocytopenia • ABL1

Asciminib vs Dasatinib/Nilotinib as First-Line Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: A Propensity Score-Matched Analysis of Disease Progression and Safety Outcomes (SOHO 2026) - "The primary end point was disease progression between days 90 and 270, defined as escalation to ponatinib or omacetaxine, hematopoietic stem cell transplantation, or transformation to acute leukemia. The progression difference did not reach statistical significance, partly reflecting insufficient power to detect a moderate effect. Retrospective claims-level ascertainment of progression is imperfect, as some therapy switches may not represent true disease advancement. The cytopenia reduction with asciminib was substantial and statistically significant."

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

Efficacy of Olverembatinib in Patients With Chronic-Phase Chronic Myeloid Leukemia With Prior Resistance to Ponatinib or Asciminib and ASXL1 Mutations (SOHO 2026) - "These data provide evidence of olverembatinib activity in ponatinib-/asciminib-resistant CP-CML, including patients with ASXL1 mutations. This agent may offer a therapeutic option for patients with relapsed/refractory CP-CML and challenging genotypes after multiple TKIs. ASXL1: ASXL transcriptional regulator 1, BCR:: ABL1: breakpoint cluster region–Abelson 1, TKI: tyrosine kinase inhibitor."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1 • BCR

ARTIST: Asciminib Frontline Risk Adapted (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Prof. Dr. med. Andreas Hochhaus

New P2 trial • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

ASC4FIRST, a Pivotal Phase 3 Study of Asciminib (ASC) vs Investigator-Selected Tyrosine Kinase Inhibitors (IS-TKIs) in Newly Diagnosed Patients With Chronic Myeloid Leukemia (CML): Primary Results (SOHO 2024) - P3 | " Adults with newly diagnosed CML were randomized 1:1 to receive ASC 80 mg once daily or an IS-TKI at standard label doses, stratified by ELTS risk category and prerandomization selected (PRS)-TKI (imatinib [IMA] or second-generation [2G] TKIs). ASC showed superior efficacy and favorable safety/tolerability vs all current standard-of-care frontline treatment."

Clinical • P3 data • Chronic Myeloid Leukemia • Oncology

A Novel BCR::ABL1 I502 T Mutation Associated With Acquired Asciminib Resistance in Chronic-Phase Chronic Myeloid Leukemia (SOHO 2026) - "Case: A 41-year-old woman with CP-CML was initially treated with imatinib for 5 years before transitioning to nilotinib for molecular relapse...Critically, I502 T retained sensitivity to dasatinib (IC50 0.3 nM) and ponatinib (IC50 0.7 nM)... I502 T is a novel myristoyl pocket mutation that confers high-level asciminib resistance while retaining sensitivity to ATP-competitive TKIs, further expanding the landscape of resistance at this critical drug-binding interface. ATP: adenosine triphosphate, BCR::ABL1: breakpoint cluster region–Abelson murine leukemia viral oncogene homolog 1, ERK: extracellular signal-regulated kinase, IC50: half-maximal inhibitory concentration, S6: ribosomal protein S6, STAT5: signal transducer and activator of transcription 5, VAF: variant allele frequency, WT: wild-type."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • RPS6 • STAT5

Ischemic Priapism as the Initial Manifestation of Chronic Myeloid Leukemia: Successful Transition to Asciminib After Dasatinib-Induced Severe Pulmonary Hypertension (SOHO 2026) - "After initial cytoreduction with hydroxyurea, he was started on dasatinib. This case highlights priapism as a dramatic hyperviscosity-related presentation of CML-CP. Prompt TKI therapy achieved deep molecular response, while timely transition to asciminib maintained excellent disease control after serious dasatinib-related cardiopulmonary toxicity. Vigilant cardiopulmonary monitoring is crucial in patients on second-generation TKIs."

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

A Phase I Study of Asciminib (ABL001) in Combination with Dasatinib and Prednisone for BCR-ABL1-Positive ALL and Blast Phase CML in Adults (ASH 2023) - P1 | "Both patients with imatinib-refractory CML-LBC progressed (C9, C3). Of those with ALL, 8 bridged to SCT after 2-8 cycles; 2 elected local care (C5, C7); 1 transitioned to ponatinib for inadequate response plus recurrent DAS pulmonary toxicity (C4); 6 remained on study treatment until disease progression (C4 – MRD+, C45, C11, C11); 3 remain on study... Dual ABL1 kinase inhibition with ASC and DAS plus pred in BCR::ABL1+ ALL and CML-LBC is feasible and tolerable in adults with BCR::ABL1+ ALL and CML-LBC. DLTs at ASC 160 mg/d were asymptomatic amylase and lipase elevation, without clinical sequelae. ASC 80 mg/day was declared the RP2D, and an expansion cohort of 10 pts was completed."

Clinical • Combination therapy • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • Pancreatitis • ABL1 • BCR

Olverembatinib After Failure of Tyrosine Kinase Inhibitors, Including Ponatinib or Asciminib: A Phase 1b Randomized Clinical Trial. (PubMed, JAMA Oncol) - P1 | "Olverembatinib may provide a viable new treatment option for patients after failure of 2 or more TKIs. ClinicalTrials.gov Identifier: NCT04260022."

Clinical • Journal • P1 data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia • ABL1 • BCR