Nailike (olverembatinib) / Ascentage Pharma, Innovent Biologics, Takeda - LARVOL DELTA

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Can Be Treated With Chemotherapy-Free Regimens Without Transplant. (PubMed, Clin Lymphoma Myeloma Leuk) - "Outcomes were significantly improved with the combination of blinatumomab and ponatinib...Combinations of newer TKIs (such as asciminib or olverembatinib) with blinatumomab (intravenous, subcutaneous) might further improve outcomes and are being explored. Achieving durable NGS MRD negativity can identify patients at low risk of relapse who might be candidates for treatment discontinuation. In this review, we discuss the current progress in the management of Ph-positive ALL, particularly the role of chemotherapy-free regimens in mitigating the need for HSCT."

Journal • Review • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1 • IKZF1

Management of chronic myeloid leukemia in 2025. (PubMed, Cancer) - "Today, the six approved BCR::ABL1 TKIs, five in frontline therapy (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and all six in later line therapy (including ponatinib), fulfill in one form or another these requirements. Third-generation TKIs that target the ABL1 kinase domain (olverembatinib and ELVN-001) or the myristoyl pocket (TGRX-678 and TERN-701) are under development...However, serious complications, such as graft-vs-host disease, or death could occur. This review summarizes relevant information concerning the management of CML in 2025, and addresses some CML treatment pathways that became entrenched in the management of CML in the first 15-20 years of TKI experience, which may need to be revisited."

Journal • Review • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • ABL1

Concomitant T315I and E459K mutations in chronic myeloid leukemia: A case report. (PubMed, Oncol Lett) - "CML with the T315I mutation alone and in combination with other mutations has demonstrated sensitivity to olverembatinib, a third-generation tyrosine kinase inhibitor, providing valuable insights into potential treatment strategies for this rare mutational profile. In the present study, a 57-year-old woman with a 7-year history of CML relapsed 1 year after stopping imatinib treatment...Laboratory tests and bone marrow analysis confirmed CML in the chronic phase, and the patient initially responded well to dasatinib...Overall, patients with multiple mutations in CML tend to have a worse prognosis due to treatment resistance and disease progression. NGS is crucial for detecting low-frequency mutations and allo-HSCT also serves a key role in treating high-risk cases."

Journal • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Musculoskeletal Pain • Oncology • Pain • Transplantation • ASXL1 • BCR

Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial. (PubMed, Leukemia) - P2 | "In conclusion, our study provides an alternative treatment strategy for patients with ND Ph+ ALL, particularly for those who are unfit or unavailable for immunotherapy or intensive chemotherapy at the initial stage of treatment. Clinical trial registration: The study was registered at https://clinicaltrials.gov/ with the registration number of NCT05594784."

Journal • P2 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial (Nature) - P2 | N=79 | NCT05594784 | "From October 2022 to March 2024, a total of 79 patients with a median age of 42 years completed a minimum of three cycles of olverembatinib and venetoclax-based regimen. The primary end point of the study was the complete molecular response (CMR) rate at 3 months. Ultimately, the regimen achieved CMR of 62.0% at 3 months in the absence of intensive chemotherapy or immunotherapy. No deaths occurred during the induction phase. With a median follow-up of 12 months, the estimated 1-year overall survival (OS) and event-free survival (EFS) rates were 93.1% (95% CI 86.4–99.8) and 89.1% (95% CI 80.3–97.9), respectively. Transcriptomic data revealed a potential complementary mechanism between TKIs and venetoclax, thereby verifying the rationale for the combination of these two agents."

P2 data • Acute Lymphocytic Leukemia

Identification of Olverembatinib as a Potential Inhibitor for ROR1+ Triple-negative Breast Cancer (EACR 2025) - "This study highlights Olverembatinib as a promising ROR1 inhibitor with strong and persistent interactions, making it a viable lead compound for further preclinical validation and development of targeted therapies against ROR1-driven triple-negative breast cancers."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ROR1

ALTERNATING LOW-DOSE INOTUZUMAB OZOGAMICIN AND BLINATUMOMAB IN MAINTENANCE THERAPY FOR PH+ALL: A SINGLE-CENTER RETROSPECTIVE ANALYSIS (EHA 2025) - "Two patients achieved MRD-CR with olverembatinib combined with Blinatumomab, while the other two achieved MRD-CR at 3 months with Flumatinib combined with chemotherapy. The alternating maintenance therapy regimen of low-dose CD19/CD3 bispecific antibody (Blinatumomab) and CD22 antibody-drug conjugate (Inotuzumab Ozogamicin), combined with continuous TKI, demonstrated promising efficacy and safety in PH+ALL patients, achieving long-term MRD-negative complete remission with a low treatment burden. Inotuzumab Ozogamicin has been widely used in Relapsed/Refractory ALL. In this study, its innovative application in low-dose maintenance therapy for MRD-negative patients represents a significant advancement."

Retrospective data • Acute Lymphocytic Leukemia • CD22

EFFICACY AND SAFETY OF BLINATUMOMAB IN NEWLY-DIAGNOSED PATIENTS WITH PH-POSITIVE/NEGATIVE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2025) - "All patients were treated with a course of 14-day or 28-day blinatumomab therapy with Ph+ patients receiving Dasatinib or Olverembatinib (third-generation tyrosine kinase inhibitor) throughout the treatment. The study demonstrates that compared with traditional induction chemotherapy, blinatumomab has showed favorable efficacy and safety in patients with Ph+/- status and high-risk genetic features. However, the relationship between blinatumomab and CNS relapse warrants further investigation."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • IKZF1 • PAX5 • TP53

EFFICACY AND SAFETY OF REGIMEN WITH OLVEREMBATINIB AND BLINATUMOMAB FOR THE FRONTLINE TREATMENT OF PH-POSITIVE OR PH-LIKE ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2025) - "This study presents the first clinical experience with the combination of olverembatinib and blinatumomab as a chemotherapy-free treatment regimen for patients with Ph-positive or ABL-class Ph-like ALL. The findings demonstrate excellent efficacy, rapid achievement of CMR, and an optimal safety profile, with no dose interruptions or cardiovascular toxicities observed. These results strongly suggest that this regimen represents a promising chemotherapy-free treatment option for patients with Ph-positive ALL."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

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

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

Olverembatinib in chronic myeloid leukemia: is less actually better? (PubMed, Haematologica) - "Not available."

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

CLINICAL FEATURES AND GENETIC ABNORMALITIES PREDICT OUTCOMES IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN THE ACCELERATED-PHASE RECEIVING OLVEREMBATINIB THERAPY: A RETROSPECTIVE MULTICENTER STUDY (EHA 2025) - "Harboring RUNX1 or STAT5A mutation, and/or complex karyotype were correlated with inferior outcomes in patients with CML-AP receiving olverembatinib therapy besides adverse clinical prognostic variables including failure to achieve CHR on prior TKI therapy, longer interval from diagnosis of CML to starting ovlerembatinib therapy, anemia, higher blasts, and not achieving early cytogenetic response on ovlerembatinib therapy."

Biomarker • Retrospective data • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • ASXL1 • DNMT3A • IKZF1 • KMT2C • RUNX1 • STAT5 • STAT5AWqe

A REAL-WORLD STUDY OF OLVEREMBATINIB IN THE TREATMENT OF CHRONIC MYELOID LEUKEMIA FROM CHINA: A SINGLE-CENTER RETROSPECTIVE STUDY (EHA 2025) - "6 patients received combined treatment, including 1 in CP (with interferon), 5 in BP (1 with interferon, 3 with venetoclax, and 1 with VP chemotherapy). Compared with clinical trials, the baseline conditions of patients treated with olverembatinib in the real world vary greatly. Under different baseline conditions, more patients can still achieve a good treatment response, but thrombocytopenia is still a hematological adverse reaction that needs to be vigilant and may be the main reason for dose adjustment. Late initiation of medication and failure to adhere to medication may be more related to poor prognosis."

Real-world • Real-world evidence • Retrospective data • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Thrombocytopenia • ABL1

COMBINATION OF OLVEREMBATINIB AND VP REGIMEN AS FIRST-LINE THERAPY FOR ADULT PATIENTS WITH PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA: A SINGLE-ARM, MULTICENTRE, PHASE 2 TRIAL (EHA 2025) - "The upfront use of third generation TKI ponatinib has improved the frequency of complete molecular response (CMR) and the survival rate...They received three cycles of olverembatinib and VP regimen(for 28 days each cycle :olverembatinib 40mg qod d1-28,Vindesine 4mg d1,8,15,22,Prednisone1mg/Kg/d1-21,0.5mg/kg/d22-28).Twelve intrathecal injections of cytarabine alternating with methotrexate were designed as entral nervous system prophylaxis in the following therapy after the diagnosis.40 patients were screened and 37 were eligible from June 21, 2022 until Feb 22, 2024... OVP regimen is effective in achieving early high rate of CMR with newly diagnosed Ph+ALL patients as first-line therapy. All these early results were achieved with surprisingly few toxic effects and well tolerance. we need more time to observe long-term outcomes.More samples are required in future studies."

Clinical • P2 data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • ABL1 • BCR

EFFICACY AND SAFETY OF THE THIRD-GENERATION TYROSINE KINASE INHIBITOR OLVEREMBATINIB IN COMBINATION WITH INOTUZUMAB OZOGAMICIN FOR THE TREATMENT OF ADULT PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS WITH RELAPSED DISEASE OR PERSISTENT MINIMAL RESIDUAL DISEASE BRIDGING TO HEMATOPOIETIC STEM CELL TRANSPLANTATION: A PHASE II STUDY (EHA 2025) - P=N/A | "The findings of this study suggest that in Ph+ ALL patients with disease recurrence and persistent MRD positivity, the combination of olverembatinib and INO has a profound molecular response rate and is well tolerated in patients with MRD clearance prior to allo-HSCT."

Clinical • Combination therapy • Minimal residual disease • P2 data • Residual disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Central Nervous System Leukemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Lymphoma • Oncology • Transplantation • ABL1 • BCR • CD22

INTEGRATING GENOMIC AND TRANSCRIPTOMIC INSIGHTS FOR PREDICTING RESPONSES AND OUTCOMES IN PATIENTS WITH CML RECEIVING 3RD-GENERATION TKI THERAPY (EHA 2025) - "Data on CML-CP and AP patients receiving ponatinib or olverembatinib were collected. This study identifies genomic, transcriptomic and immune determinants of 3G-TKI responses and outcomes in CML. Our findings established the GEPs-based classification as a robust independent predictor, outperforming clinical and genomic features. These insights provide a basis for improved patient stratification."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ASXL1 • CD4 • CD8 • GATA2 • IKZF1 • PBRM1 • PHF6 • RUNX1 • SETBP1 • TNFA • TNFAIP3

EFFICACY AND SAFETY OF THE THIRD-GENERATION TKI OLVEREMBATINIB IN RELAPSED AND PERSISTENT MRD POSITIVE PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS (EHA 2025) - "Olverembatinib has shown significant efficacy in improving both hematologic responses and laboratory parameters. Although the incidence of adverse events is notable, real-world clinical data reveal that the majority of patients maintain sufficient treatment tolerance. These collective findings underscore that Olverembatinib represents a safe and effective therapeutic option for relapsed and persistent MRD positive Ph+ALL patients."

Clinical • Minimal residual disease • Acute Lymphocytic Leukemia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Endocrine Disorders • Infectious Disease • Leukopenia • Myocardial Infarction • Pneumonia • Respiratory Diseases

A PHASE 2 STUDY OF OLVEREMBATINIB FOR THE TREATMENT OF MYELOID/LYMPHOID NEOPLASMS WITH FGFR1 REARRANGEMENT (EHA 2025) - "Pemigatinib, a selective inhibitor of FGFR1-FGFR3, has shown remarkable complete remission (CR) rates and complete cytogenetic remission (CCyR) in patients(pts) with chronic-phase (CP) disease but poorer responses in those with blast-phase (BP) disease...Beyond its use in Philadephia-chromosome positive leukemia, olverembatinib has demonstrated antitumor activity in FGFR1-mutated cells in parallel to ponatinib...10 pts (76.9%) achieved CR/CHR, among whom 1 achieved CCyR (Pt 04 who received olverembatinib alone) and 1 achieved CMR (Pt 08 who received olverembatinib combined with inotuzumab ozogamicin) at 2 months' evaluation... Olverembatinib showed a favorable CR/CHR rate and good tolerance in the treatment MLN-FGFR1, potentially enabling allo-HSCT in greater numbers of eligible patients."

P2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Eosinophilia • Fatigue • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Musculoskeletal Pain • Oncology • Pain • FGFR1 • FGFR3 • RUNX1 • ZMYM2

SYNERGISTIC EFFECTS OF OLVEREMBATINIB (HQP1351) COMBINED WITH BCL-2 INHIBITOR LISAFTOCLAX (APG-2575) AND BCL-2/BCL-XL INHIBITOR PELCITOCLAX (APG-1252) IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (T-ALL) (EHA 2025) - "Molecular mechanisms of action were assessed by western blotting.In both T-ALL cell lines, olverembatinib in combination with lisaftoclax or APG-1244 exhibited synergistic antiproliferative effects compared with single agents. Olverembatinib in combination with lisaftoclax and/or pelcitoclax demonstrated synergistic antitumor effects in T-ALL, providing a scientific rationale for further clinical evaluation of this novel combination therapy in patients with this condition."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ANXA5 • BCL2L1 • CASP3 • MCL1 • MYC

A Phase 2 Study of Olverembatinib for the Treatment of Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement (GlobeNewswire) - P2 | N=20 | NCT05521204 | "Highlights of select abstracts presented at EHA 2025 are as follows....Results show that in the 13 patients who were analyzed for efficacy, 10 (76.9%) achieved CR/complete hematologic response (CHR), among whom 1 achieved complete cytogenetic response (CCyR, by a patient who received olverembatinib alone) and 1 patient achieved CMR at 2 months’ evaluation. In this study, olverembatinib showed a promising CR/CHR rate and favorable tolerability in MLN-FGFR1, potentially enabling allo-HSCT in greater numbers of eligible patients. These findings revealed an effective targeted therapy for MLN-FGFR1, a rare hematologic malignancy with a poor prognosis that currently lacks standard-of-care treatment."

P2 data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia

Efficacy and Safety of the Third-Generation Tyrosine Kinase Inhibitor Olverembatinib in Combination with Inotuzumab Ozogamicin for the Treatment of Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients With Relapsed Disease or Persistent Minimal Residual Disease Bridging to Hematopoietic Stem Cell Transplantation: A Phase II Study (GlobeNewswire) - P2 | N=46 | NCT05603156 | "Highlights of select abstracts presented at EHA 2025 are as follows....This is an open-label, single-center Phase II study that evaluated the efficacy and safety of olverembatinib in combination with inotuzumab ozogamicin (INO) in patients with Ph/BCR-ABL1+ ALL who had relapsed or persistent MRD after at least three rounds of chemotherapy. Results from this study show that after receiving the treatment, all patients achieved hematologic CR, 11 patients achieved CMR, with an overall CMR rate of 78.6% and an MRD-negativity rate of 100%. 64.3% (n=9) of patients successfully underwent bridged allogeneic hematopoietic stem cell transplantation (allo-HSCT). The 2-year OS and relapse-free survival (RFS) rates were 88.2 ± 15.2% and 62.9 ± 17.9%, respectively."

P2 data • Acute Lymphocytic Leukemia

Combination of Olverembatinib and VP Regimen as First-Line Therapy for Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Single-Arm, Multicentre, Phase 2 Trial (GlobeNewswire) - P2 | N=37 | "Highlights of select abstracts presented at EHA 2025 are as follows....This single-arm, multicenter Phase II study assessed the efficacy and safety of olverembatinib in combination with the VP (vindesine+prednisone) regimen (OVP) in the first-line treatment of adult patients with Ph+ ALL. Results from this study showed that in patients treated with the OVP induction therapy, the overall response rate (ORR) was 100%, the CR rate was 97.3%, and 89.2% (33/37) of patients achieved CMR within 3 treatment cycles. The 2-year OS and progression-free survival (PFS) rates were 96.3% and 96%, respectively. These findings suggest that the OVP regimen is effective in achieving a high CMR rate in the early treatment of patients with newly diagnosed Ph+ ALL..."

P2 data • Acute Lymphocytic Leukemia

Efficacy and Safety of Regimen with Olverembatinib and Blinatumomab for the Frontline Treatment of Ph-Positive or Ph-Like Acute Lymphoblastic Leukemia (GlobeNewswire) - P=NA | N=24 | "Highlights of select abstracts presented at EHA 2025 are as follows....Results from this study show that with a median follow-up duration of 17 months, all patients achieved CR following one cycle of treatment. At 18 months, the overall survival (OS) rate was 100% and the event-free survival (EFS) rate was 91.6%. The regimen was well tolerated and no patient experienced cardiovascular events. Notably, administration of olverembatinib and blinatumomab was not interrupted throughout the treatment course with no dose reduction required. These findings suggest that the combination of olverembatinib and blinatumomab offers promising clinical benefits and an optimal safety profile in patients with Ph+ or Ph-like ALL..."

Clinical data • Acute Lymphocytic Leukemia