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

Olverembatinib Combined With Venetoclax and Azacitidine in Blast Phase Ph Chromosome-positive CML (clinicaltrials.gov) - P1/2 | N=29 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting ➔ Recruiting

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

Olverembatinib for heavily pretreated BCR::ABL1-positive leukemia, including resistance or intolerance to ponatinib and/or asciminib. (PubMed, Ann Transl Med) - No abstract available

Journal • Hematological Malignancies • Leukemia • Oncology • ABL1

Olverembatinib (HQP1351)-based therapy in adults with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia in blast phase: results from a real-world study. (PubMed, Front Immunol) - "Additionally, 19 patients (33.9%) had been treated with ponatinib. The prevalent treatment-related nonhematologic adverse events, primarily classified as grade 1/2, included skin hyperpigmentation, proteinuria, increased liver enzyme levels, and hypertriglyceridemia. Olverembatinib-based therapy demonstrated significant efficacy and manageable toxicity in patients with advanced Ph+ leukemia."

Journal • Real-world evidence • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Dyslipidemia • Hematological Malignancies • Hypertriglyceridemia • Renal Disease • ABL1 • BCR

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

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

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

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 • Cardiovascular • Chronic Myeloid Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • 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

Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia with e13a3 fusion transcripts in a patient with pre-existing essential thrombocythemia: a case report and literature review. (PubMed, Front Oncol) - "Following four cycles of induction therapy with olverembatinib, vincristine, and prednisone, the patient achieved complete hematologic and molecular remission. A chemotherapy-free consolidation therapy with olverembatinib and blinatumomab maintained sustained complete molecular remission at follow-up. To our knowledge, this represents the first case of Ph-positive B-ALL with e13a3 transcripts arising in a patient with preexisting ET, providing critical therapeutic insights for managing similar cases."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Essential Thrombocythemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • Thrombocytosis • ABL1 • BCR • CALR • JAK2 • MPL

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 • Cardiovascular • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • ASXL1 • DNMT3A • IKZF1 • KMT2C • RUNX1 • STAT5 • STAT5AWqe

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

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 • Cardiovascular • Hematological Malignancies • Leukemia • Oncology

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

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 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

Effects of olverembatinib (HQP1351) in combination with BCL-2 inhibitor lisaftoclax (APG-2575) in T-cell acute lymphoblastic leukemia (T‑ALL) (AACR 2025) - "Olverembatinib in combination with lisaftoclax demonstrated synergistic antitumor effects in T-ALL, providing a scientific rationale for further clinical evaluation of this novel combination therapy in patients with T-ALL."

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

Optimizing olverembatinib dose in chronic phase chronic myeloid leukemia. (PubMed, Haematologica) - "Also, the proportion of subjects receiving a reduced dose or permanently discontinuing because of adverse event was significantly lower in the 30 mg cohort (21% [9, 33%] versus 41% [34, 48%]; p = 0.003). In summary, olverembatinib, 30 mg QOD starting dose is as effective as a 40 mg starting dose but better tolerated in persons with chronic phase CML failing other TKIs."

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

Effects of olverembatinib (HQP1351) in combination with Bcl-2 inhibitor lisaftoclax (APG-2575) in T-cell acute lymphoblastic leukemia (T-ALL) (GlobeNewswire) - "Olverembatinib in combination with lisaftoclax synergistically inhibited proliferation and augmented apoptosis in T-ALL cells in vitro. The combination synergistically suppressed tumor growth in a MOLT4 xenograft model in vivo. Mechanistically, olverembatinib inhibited Lck phosphorylation, and when combined with lisaftoclax, synergistically reduced downstream NF-kB p65 and BCL-xL, which is typically upregulated in T-ALL. The combination also downregulated phosphorylation of AKT and GSK3b kinases, resulting in degradation of MCL-1 and c-MYC, an essential pro-oncogenic protein in T-ALL."

Preclinical • T Acute Lymphoblastic Leukemia

Olverembatinib (HQP1351) in combination with lisaftoclax (APG-2575) overcomes venetoclax resistance in preclinical models of acute myeloid leukemia (AML) (AACR 2025) - "In summary, olverembatinib in combination with lisaftoclax successfully overcame venetoclax resistance in preclinical AML models by downregulating key signaling pathways shown to mediate such resistance. Overall, these findings suggest a potential new therapeutic strategy for venetoclax-resistant AML."

Combination therapy • IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CASP3 • FGFR • FLT3 • MCL1

ASCENTAGE PHARMA ANNOUNCES INCLUSION OF LISAFTOCLAX AND OLVEREMBATINIB IN CHINESE SOCIETY OF CLINICAL ONCOLOGY (CSCO) 2025 GUIDELINES (HKEXnews) - "Ascentage Pharma Group International...is pleased to announce that two of its proprietary novel drugs have been included in the 2025 Chinese Society of Clinical Oncology (CSCO) Guidelines. Lisaftoclax (APG-2575), the Company’s investigational novel oral Bcl-2 selective inhibitor, received its first recommendation in the CSCO Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies. Olverembatinib, the Company’s novel next-generation tyrosine kinase inhibitor (TKI), received an upgraded recommendation in the CSCO Guidelines for the Diagnosis and Treatment of Leukemias in Children and Adolescent, and retained its recommendations in the CSCO Guidelines for the Diagnosis and Treatment of Hematological Malignancies."

Clinical guideline • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Small Lymphocytic Lymphoma

Olverembatinib (HQP1351) in combination with lisaftoclax (APG-2575) overcomes venetoclax resistance in preclinical models of acute myeloid leukemia (AML) (GlobeNewswire) - "In VEN-R AML cell lines, the combination of olverembatinib and lisaftoclax synergistically inhibited cellular proliferation and induced cellular apoptosis. Olverembatinib in combination with lisaftoclax synergistically suppressed tumor growth in a MOLM-13-VEN-R AML xenograft model in vivo. Mechanistically, western blot analysis revealed that the combination synergistically downregulated several leukemogenic signaling pathways, including those associated with venetoclax resistance, such as FLT3, AKT, MCL-1, and activated apoptosis."

Preclinical • Acute Myelogenous Leukemia

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

Blinatumomab in combination with olverembatinib and concurrent intrathecal chemotherapy successfully treated a chronic myeloid leukemia relapse with central nervous system blast crisis: case report and literature review. (PubMed, Ann Hematol) - "The combination of blinatumomab, olverembatinib, and concurrent intrathecal chemotherapy may be an effective treatment strategy for CML progression, particularly in cases with CNS involvement."

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

IMPROVED OUTCOMES FOR PEDIATRIC PATIENTS WITH DE NOVO CHRONIC MYELOID LEUKEMIA IN BLAST PHASE BY EARLY STAGE ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (EBMT 2025) - "Four patients were treated with VDLP and dasatinib, while one received VP with venetoclax and olverembatinib...Two patients received haploidentical transplants with treosulfan, busulfan, fluorouracil, and anti-thymocyte globulin, while three received unrelated cord blood transplants with busulfan, fluorouracil, and cyclophosphamide... Differentiating CML-BP from Ph+ ALL at early stage is crucial as distinct therapy is recommended. FISH aids in differentiation diagnosis. Early HSCT significantly improves their outcomes, though extended follow-up and more participants are needed to validate these findings."

Clinical • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Pediatrics • Transplantation • ABL1