nilotinib / Generic mfg. - LARVOL DELTA

Asciminib (ASC) Demonstrates Favorable Safety and Tolerability Compared with Each Investigator-Selected Tyrosine Kinase Inhibitor (IS TKI) in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Pivotal Phase 3 ASC4FIRST Study (ASH 2024) - "Introduction : About 1/3rd of patients (pts) with newly diagnosed CML discontinue/switch treatments (Tx) regardless of TKI (imatinib [IMA], nilotinib [NIL], dasatinib [DAS], or bosutinib [BOS]). ASC's superior efficacy vs all IS TKIs and more favorable safety/tolerability compared with each IS TKI (IMA, NIL, DAS, and BOS) suggests that ASC may transform the CML Tx paradigm. Key secondary endpoints, including MMR rate at wk 96, and other long-term secondary efficacy and safety/tolerability results, will be presented at ASH 2024."

Clinical • P3 data • Atherosclerosis • Cardiovascular • Chronic Myeloid Leukemia • Congestive Heart Failure • Coronary Artery Disease • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myocardial Infarction • Oncology • Pancreatitis • Respiratory Diseases • Thrombocytopenia

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

Treatment-free remission after two nilotinib consolidation durations in chronic myeloid leukemia treated with imatinib: Phase 3 ENESTPath results. (PubMed, Leukemia) - "In the TFR phase, MR4.0 rates at 12 months (Arm 1: 31.9%, Arm 2: 37.5%; p = 0.383) and 24 months (Arm 1: 29.4%, Arm 2: 30.8%) revealed no differences in TFR success between 2 and 3 years of nilotinib. Irrespective of the consolidation duration, switching to nilotinib 300 mg BID provided the opportunity to achieve TFR if patients were unable to reach stable DMR with first-line imatinib."

Journal • P3 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Efficacy of Bidirectional Paclitaxel plus Capecitabine or Nilotinib for Peritoneal Carcinomatosis: A Single Institution Analysis of Two Phase II Clinical Trials. (PubMed, Ann Surg Oncol) - "Bidirectional paclitaxel-based chemotherapy plus capecitabine may delay progression of gastric adenocarcinoma with peritoneal-only metastasis. Bidirectional paclitaxel-based chemotherapy plus nilotinib was associated with mostly stable peritoneal disease in this small, heterogenous cohort. Bidirectional paclitaxel combinations are feasible and may have a role in therapy for disease stabilization in individuals with peritoneal carcinomatosis."

Journal • P2 data • Appendix Cancer • Colorectal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Peritoneal Cancer • Small Intestinal Carcinoma • Solid Tumor

Interleukin signaling mitigates the inhibitory effects of combined Src/BCR-ABL1 blockade on T-cell activity in Philadelphia chromosome-positive acute lymphoblastic leukemia. (PubMed, Haematologica) - "Consistent with prior preclinical studies, we demonstrate that dasatinib and ponatinib, unlike SRC sparing TKIs (imatinib, nilotinib), antagonize blinatumomab's T-cell engaging efficacy by potently inhibiting LCK Y394 phosphorylation, a critical step in proximal TCR signaling. We show that TKI-induced T-cell suppression and antagonism can be significantly improved by supplementing co-cultures with common gamma-chain cytokines, particularly IL-7. IL-7 robustly enhances human T-cell proliferation, reduces exhaustion, and significantly improves blinatumomab's cytotoxic efficacy in the presence of Src/BCRABL1 TKIs."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • IL7

A novel case of nilotinib-induced porphyria cutanea tarda (AAD 2026) - No abstract available

Clinical • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Rare Diseases

ASO Visual Abstract: Efficacy of Bidirectional Paclitaxel Plus Capecitabine or Nilotinib for Peritoneal Carcinomatosis: A Single-Institution Analysis of Two Phase II Clinical Trials. (PubMed, Ann Surg Oncol) - No abstract available

Journal • P2 data • Oncology • Peritoneal Cancer

OPTIMIZING TRANSPLANT OUTCOMES IN PHILADELPHIA CHROMOSOME–POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA WITH PRE-TRANSPLANT SECOND- AND THIRD-GENERATION TKIS AND POST-TRANSPLANT PROPHYLACTIC MAINTENANCE: A STUDY FROM THE EBMT ALWP (EBMT 2026) - "Peripheral blood stem cells were used in 84% of cases, with 79% receiving myeloablative conditioning, and 51% receiving total body irradiation.TKI use prior to transplant included imatinib (N=612, 64%), dasatinib (N=210, 22%), nilotinib (N= 96, 10%), and ponatinib (N=40, 4%). In this large, multicenter cohort of patients with Ph+ ALL undergoing allo-HCT in CR1, the use of second- and third-generation TKIs during induction was associated with superior survival outcomes compared to imatinib. Post-transplant TKI prophylaxis significantly improved survival regardless of pre-transplant MRD status. These findings support the incorporation of newer TKIs and prophylactic strategies in the transplant setting to optimize long-term outcomes in Ph+ ALL."

Clinical • Post-transplantation • Pre-transplantation • Acute Lymphocytic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation

OLVEREMBATINIB-MEDIATED DEEP REMISSION IMPROVES ALLOGENEIC STEM CELL TRANSPLANTATION OUTCOME IN PATIENTS WITH BLAST CRISIS CHRONIC MYELOID LEUKEMIA: THE FIRST REAL-WORLD PRACTICE (EBMT 2026) - "All patients received TKIs+chemotherapy before transplantation and were stratified by pre-transplant TKIs exposure: 1/2G-TKI cohort (n=43, imatinib, nilotinib, flumatinib or dasatinib) versus olverembatinib (n=26). This real-world analysis provides the first clinical evidence supporting the efficacy and safety of olverembatinib in transplant-eligible BC-CML. Olverembatinib significantly enhances pre-transplant molecular responses, compared to 1/2G-TKIs, associating with improved survival after transplantation. With a manageable safety profile, olverembatinib represents a promising bridging strategy prior to allo-HSCT, potentially redefining frontline management of BC-CML."

Clinical • Real-world • Real-world evidence • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Transplantation • ABL1 • ASXL1 • IKZF1 • RUNX1

THIRD-LINE TREATMENT OF CHRONIC MYELOID LEUKEMIA WITH TKI IN THE POST-BMT SETTING IN PATIENT WITH POSITIVE MRD (EBMT 2026) - "Starts on Dasatinib 100 mg per day, after one year only achieves complete hematologic response (CHR), remaining qPCR BCR-ABL: 72%IS; T315I mutation by PCR: undetected. Switch of therapy with Nilotinib 800 mg per day with no molecular response in 6 months (qPCR BCR-ABL: 44%IS)...Ponatinib was again discontinued due to hematologic toxicity.Starts oh Asciminib by day 124, achieving MR 4.0 by day 195 which is maintained by day 395... This clinical case shows that there still cases of chronic myeloid leukemia resistant to second generation TKI, even with early initiation at diagnosis. Toxicity is often associated with resistance. In our case, starting Ascminib as maintenance treatment post BMT, instead of Ponatinib due to hematologic and cardiologic toxicity, had a major impact on response achieving MR 4.0 sustained with no toxicity associated."

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

ALLOGENEIC TRANSPLANTATION OUTCOMES OF PHILADELPHIA-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA WITH OR WITHOUT ADDITIONAL CYTOGENETIC ABNORMALITIES AND COMPLEX KARYOTYPE: A STUDY FROM THE ALWP/EBMT (EBMT 2026) - " 514 Ph+ pts that received TKI (Imatinib-62%, Dasatinib-17.7%, Nilotinib-13.3%, other-7%) followed by HSCT while CR1 between 2010-2022 were included. Harboring ACA and CK did not affect outcomes of Ph+ ALL pts receiving a TKI and subsequent HSCT. Notably, achieving MRD-negativity pre HSCT was significantly higher in pts with ACA. These data may indicate that the administration of a TKI upfront, followed by HSCT, may overcome the poor prognosis influence of the ACA, including CK in Ph+ ALL."

Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation • IKZF1

Olverembatinib As Second-Line (2L) Therapy in Patients (pts) with Chronic Phase-Chronic Myeloid Leukemia (CP-CML) (ASH 2024) - P2 | "Twelve (28.6%) pts had received 1L imatinib, and 30 (71.4%) had been treated with a 1L 2G TKI, including dasatinib (n = 5, 11.9%), nilotinib (n = 11, 26.2%), or flumatinib (n = 14, 33.3%). Conclusions This is the first study report of olverembatinib in 2L CP-CML treatment. Olverembatinib may provide an effective and safe 2L treatment option for pts with CP-CML, especially those failing on 1L 2G TKIs."

Clinical • Anemia • Cardiovascular • Chronic Myeloid Leukemia • Hypertension • Neutropenia • Thrombocytopenia • ABL1 • BCR

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

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) - P2 | "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 • Anemia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Leukemia • Leukopenia • Myocardial Infarction • Neutropenia • Oncology • Thrombocytopenia • ABL1

FRONTLINE CHEMOTHERAPY-FREE COMBINATION OF OLVEREMBATINIB WITH VENETOCLAX AND AZACITIDINE IN NEWLY DIAGNOSED PH+ ACUTE LYMPHOBLASTIC LEUKEMIA:PRELIMINARY OUTCOMES OF A PROSPECTIVE STUDY (EHA 2025) - P2 | "The second-generation tyrosine kinase inhibitors (TKIs) (e.g., dasatinib, nilotinib) improved early complete remission (CR) rates to 90-95%, only 40-60% of patients achieve complete molecular response (CMR) by 3 months—a critical predictor of long-term survival. This chemotherapy-free regimen combining olverembatinib, venetoclax, and azacitidine demonstrates rapid CMR kinetics and tolerability in newly diagnosed Ph+ALL, potentially redefining frontline management. Furthermore, this regimen may represent a feasible outpatient treatment option for both induction and consolidation phases in patients with Ph+ALL, owing to its favorable tolerability."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Cardiovascular • Chronic Myeloid Leukemia • Febrile Neutropenia • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • Thrombosis • ABL1 • IKZF1

Intramolecular Interactions of Twenty-Eight Amide Derivatives with the C-ALB Kinase using a Theoretical Model as a Therapeutic Alternative to Treat Cancer. (PubMed, Drug Res (Stuttg)) - "Besides, bosutinib, dasatinib, imatinib, nilotinib, and radotinib were used as controls in the DockingServer program.The results displayed different types of aminoacid residues involved in the interaction of amide derivatives with the 1iep protein surface compared to the controls. Finally, the Ki for amide derivatives 1, 19, and 21 were lower compared with bosutinib, dasatinib, imatinib, and nilotinib.Theoretical data indicate that amide derivatives such as 1, 15, 16, 18, 19, and 21 might have a higher affinity for the 1iep protein surface. This phenomenon could be translated as c-Abl kinase inhibition, resulting in a decrease in cancer cell growth."

Journal • Oncology • ABL1

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

A phase 2 study of nilotinib in pediatric patients with CML: long-term update on growth retardation and safety. (PubMed, Blood Adv) - P2 | "The phase 2, open-label study (DIALOG) of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) met its coprimary end points, showing sustained nilotinib efficacy in patients with newly diagnosed (ND) or imatinib/dasatinib resistant/intolerant (R/I) CML. Apart from the impact on growth, the safety profile of nilotinib was generally consistent with previous reports. This study was registered on www.clinicaltrials.gov at #NCT01844765."

Clinical • Journal • P2 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pain • Pediatrics

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

Treatment of K562 Cells with ABL Kinase Inhibitors Reveals Differential Metabolic Profiles. (PubMed, Drug Res (Stuttg)) - "In the current study, using K562 cell lines, the metabolic impact of five ABL kinase inhibitors, such as imatinib, dasatinib, nilotinib, ponatinib, and axitinib, was studied. Pathway enrichment analysis identified significant downregulation in starch and sucrose metabolism, nucleotide sugar metabolism and sphingolipid metabolism. These results offered insights to guide the development of treatment strategies for overcoming the drug resistance in chronic myelogenous leukemia as well as managing the associated toxicities."

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

Mitochondrial DNA Mutations Are Associated with Impaired Mitochondrial Fitness and TKI Sensitivity in CML (LCC 2026) - "Methods and Results Total white cells from 124 CML patients at diagnosis treated with imatinib (n=80; ALLG TIDEL I/II) or nilotinib (n=44; PINNACLE/ENESTxtnd) were analysed, using remission samples or mesenchymal stem cells/hair follicles as germline controls. Seahorse analysis confirmed enhanced OXPHOS in TKI-Res cells, with higher spare respiratory capacity (126 vs 53 pmol/min/10⁵, p=0.001), while MitoTracker_green showed a modest 1.4-fold higher mitochondrial content (p=0.045). Conclusions These data support a model in which mtDNA mutations in IM-S patients impair mitochondrial fitness, whereas resistant LSPCs maintain metabolic flexibility, linking mitochondrial alterations to transcriptional reprogramming and TKI response."

Tumor mutational burden • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • TMB

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

Treatment-Free Remission in Chronic Phase Chronic Myeloid Leukemia After Nilotinib De-Escalation: 96-Week Update of the DANTE Study. (PubMed, Hematol Oncol) - "During TFR, adverse events occurred in 64 patients (71.1%), including one serious event (pneumonia). Our data suggest that the de-escalation of nilotinib before a TFR attempt in CML-CP patients with sustained DMR can be a successful dose optimization strategy."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases

A plain language summary of how the body processes a lower-dose nilotinib tablet (Danziten™) compared to the existing capsule (Tasigna®). (PubMed, Future Oncol) - No abstract available

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