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

Ph+ ALL-2026: Immunotargeted Therapy Plus Low-Dose Chemotherapy in Newly Diagnosed Adult Ph+ B-ALL (clinicaltrials.gov) - P2 | N=22 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD22

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

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 Refractory/Relapsed Disease or Persistent Minimal Residual Disease Bridging to Hematopoietic Stem Cell Transplantation. (PubMed, Am J Hematol) - No abstract available

Journal • Minimal residual disease • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Olverembatinib Combined With Blinatumomab in Patients With Lymphoid Blast Phase Chronic Myeloid Leukemia or Philadelphia Chromosome–Positive B-Cell Precursor Acute Lymphoblastic Leukemia (SOHO 2026) - P1 | "Olverembatinib plus blinatumomab shows promising activity in patients with R/R Ph+ BCP-ALL or CML-LBP, with encouraging response rates and MRD clearance, and is generally well tolerated. The data support further investigation of this chemotherapy-free approach. AEs: adverse events, ALL: acute lymphoblastic leukemia, CML-LBP: lymphoid-blast-phase chronic myeloid leukemia, CR: complete response, DLT: dose-limiting toxicity, R/R Ph+ BCP-ALL: relapsed/refractory Philadelphia chromosome–positive B-cell precursor ALL, MRD: measurable residual disease, TKI: tyrosine kinase inhibitor."

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

Olverembatinib, a multikinase inhibitor that modulates lipid metabolism, in advanced succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 1b study and translational research. (PubMed, Signal Transduct Target Ther) - P1 | "Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) are generally resistant to targeted therapy with tyrosine kinase inhibitors (TKIs), such as imatinib, and there are no standard therapeutic options for advanced SDH-deficient GISTs. As a putative mechanism of action, translational research revealed significant lipid enrichment with the overexpression of lipid uptake-related genes and proteins, including CD36, fatty acid binding proteins, fatty acid transport proteins, and lipid metabolites, in SDH-deficient GIST patients, and olverembatinib suppressed lipid uptake and CD36 expression in GIST cells. Olverembatinib also exerts antitumor effects by inhibiting tumorigenic signaling pathways associated with hypoxia, angiogenesis, proliferation, and survival."

Journal • P1 data • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hematological Disorders • Metabolic Disorders • Oncology • Sarcoma • Solid Tumor • CD36 • SCARB1

POLARIS-2: Study of Olverembatinib (HQP1351) in Patients With CML-CP (clinicaltrials.gov) - P3 | N=333 | Recruiting | Sponsor: Ascentage Pharma Group Inc. | Trial completion date: Feb 2026 ➔ Jul 2028 | Trial primary completion date: Dec 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

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

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-Based Treatment for Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Multi-Center Retrospective Study (SOHO 2026) - "Blinatumomab was applied for consolidation in 9 of 18 patients (50%). Nine of 18 (50%) patients have entered the maintenance therapy phase, of whom 6 received olverembatinib only, 2 received a combination of olverembatinib and chemotherapy, and 1 received a combination of dasatinib and chemotherapy due to financial issues... Olverembatinib-based regimen with lower-intensity chemotherapy showed promising outcomes with acceptable side effects as frontline therapy in patients with Ph+ ALL, warranting further trials to investigate better strategies. ALL: acute lymphoblastic leukemia, allo-HSCT: allogeneic hematopoietic stem cell transplantation, BCR::ABL1: breakpoint cluster region–Abelson murine leukemia viral oncogene homolog 1 fusion, CAR-T: chimeric antigen receptor T-cell, CMR: complete molecular remission, CR: complete response, IKZF1: Ikaros family zinc finger protein 1, PCR: polymerase chain reaction, Ph+: Philadelphia chromosome–positive, TKI: tyrosine kinase..."

Retrospective data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • IKZF1

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

Safety and Preliminary Efficacy of Olverembatinib (HQP1351) Combined With Lisaftoclax (APG-2575) in Children and Adolescents With Relapsed/Refractory Philadelphia-Positive Acute Lymphoblastic Leukemia: Results of a Phase 1b Study (SOHO 2026) - P1 | "Olverembatinib plus lisaftoclax induced rapid, deep remissions in pediatric R/R Ph+ ALL with manageable toxicity and favorable pharmacokinetics. This chemotherapy-free oral regimen demonstrated activity across ABL1 mutants with CNS penetration, supporting its potential in this high-risk population. ABL1: ABL proto-oncogene 1, non-receptor tyrosine kinase, ALL: acute lymphoblastic leukemia, BCL-2: B-cell lymphoma 2, BCR::ABL1: breakpoint cluster region–Abelson 1, CNS: central nervous system, CR: complete response, FISH: fluorescence in situ hybridization, MRD: measurable residual disease, T315I: threonine-to-isoleucine mutation at position 315."

Clinical • IO biomarker • P1 data • Acute Lymphocytic Leukemia • B Cell Lymphoma • Leukemia • Lymphoma • Oncology • ABL1 • BCR

Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and paraganglioma. (ASCO 2024) - P1 | "Olverembatinib was well tolerated. The CBR exceeded 90%, and the estimated median PFS was significantly prolonged, indicating potential benefit of this treatment and providing a benchmark for future studies in this rare subtype of GIST. Clinical trial registration: NCT03594422; internal study identifier: SJ-0003."

Clinical • Stroma • Chronic Myeloid Leukemia • CNS Tumor • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Hematological Malignancies • Leukemia • Oncology • Sarcoma • Solid Tumor

Olverembatinib Combined with Venetoclax and Reduced-Intensity Chemotherapy for Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Early Results from a Phase II Study (ASH 2023) - P2 | "Pts were treated with a combination of venetoclax (100 mg d1, 200 mg d2, 400 mg d3-28), olverembatinib 40 mg once every continuously other day, vincristine 1.4 mg/m2 (maximum dose 2 mg) on day 1, 8, 15, 22, and prednisone 60 mg/m2 on day 1-14; 40 mg/m2 on day 15-28 in cycle 1...Routine triple intrathecal injection (methotrexate 10 mg, cytarabine 50 mg, and dexamethasone 10 mg) was performed to prevent central nervous system involvement...Conclusion The combination of olverembatinib and venetoclax with reduced-intensity chemotherapy is a safe and effective regimen in patients with newly diagnosed Ph+ ALL. The regimen results in high rates of CMR in the absence of intensive chemotherapy or immunotherapy."

Clinical • IO biomarker • P2 data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • ABL1

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

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

Updated Results of POLARIS-1 (Part 1), a Global Registrational Phase 3 Study: Olverembatinib Combined With Low-Intensity Chemotherapy in Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (SOHO 2026) - P3 | "Induction included vincristine, dexamethasone, ±daunorubicin for 3 cycles. Consolidation alternated 3 cycles of high-dose methotrexate with 3 cycles of cytarabine; maintenance continued for 12 cycles... Olverembatinib plus reduced-intensity chemotherapy achieved 63.0% MRD-negative CR in ND Ph+ ALL, including patients with inferior prognostic genotypes, with a favorable safety profile. ALL: acute lymphoblastic leukemia, BCR::ABL1: breakpoint cluster region–Abelson 1, CR: complete response, CRi: complete response with incomplete blood count recovery, ECOG PS: Eastern Cooperative Oncology Group performance status, EOI: end of induction, HSCT: hematopoietic stem cell transplantation, MRD: measurable residual disease, ND: newly diagnosed, Ph+: Philadelphia chromosome–positive, qPCR: quantitative polymerase chain reaction, TEAE: treatment-emergent adverse event. Funding: Ascentage Pharma Group Corp Ltd (Hong Kong)."

Clinical • P3 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • IKZF1

Updated efficacy results of olverembatinib (HQP1351) in patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and potential mechanisms of action (MOA) (ESMO 2024) - P1, P2 | "Olverembatinib showed sustained clinical efficacy in SDH-deficient GIST, indicating potential benefit of this treatment and providing a benchmark for future studies in this rare subtype of GISTs. MOA studies revealed that olverembatinib exerts antitumor activity by modulating multiple signaling pathways involved in angiogenesis, apoptosis, proliferation, and survival."

Clinical • Stroma • Endocrine Cancer • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • EPAS1 • FGFR1 • SDHB

A new chemotherapy-free regimen of olverembatinib in combination with venetoclax and dexamethasone for newly diagnosed Ph+ acute lymphoblastic leukemia: Preliminary outcomes of a prospective study. (PubMed, Am J Hematol) - No abstract available

Combination therapy • Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Patient-reported outcomes in adults with tyrosine kinase inhibitor-resistant chronic myeloid leukemia receiving olverembatinib therapy. (PubMed, Cancer) - "The authors concluded that HRQoL significantly improved over time during olverembatinib therapy in heavily treated patients with TKI-resistant CML, especially among those who were younger and those who had CML-CP. Anxiety symptoms also significantly decreased over time."

Journal • Patient reported outcomes • Chronic Myeloid Leukemia • CNS Disorders • Depression • Fatigue • Hematological Malignancies • Leukemia • Mood Disorders • Oncology • Psychiatry • Pulmonary Disease

Safety and Efficacy of Tgrx-678, a Potent BCR-ABL Allosteric Inhibitor in Patients with Tyrosine Kinase Inhibitor (TKI) Resistant/Refractory Chronic Myeloid Leukemia (CML): Preliminary Results of Phase I Study (ASH 2023) - P1 | "There were 22 CML-CP and 23 CML-AP patients previous received 3rd Gen TKIs (ponatinib or HQP1351) or asciminib. Clinical activity of TGRX-678 was seen in all cohorts and across TKI-resistant mutations including T315I, providing a promising treatment option for CML CP/AP patients, including those who failed ponatinib or asciminib. Its unique PK properties might bring additional benefit to patients. TGRX-678 was well tolerated in heavily pretreated CML patients."

Clinical • P1 data • Anemia • Chronic Myeloid Leukemia • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Leukemia • Neutropenia • Oncology • Thrombocytopenia • ABL1 • BCR

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

Reframing chronic myeloid leukemia outcomes beyond survival: a perspective of quality of life and patient-centered data. (PubMed, Blood Rev) - "Commonly used TKIs (imatinib, nilotinib, dasatinib, bosutinib, ponatinib, asciminib, and olverembatinib) all have positive and negative impacts on QoL, each of which can be impacted by patient preference and priorities, as well as line of therapy. The inclusion of patient-reported QoL outcomes in clinical trials will be vital to helping physicians understand the patient experience of CML and thereby improve disease management."

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

Olverembatinib (HQP1351) combined with blinatumomab in patients with lymphoid blast phase chronic myeloid leukemia (CML-LBP) or Philadelphia chromosome–positive B-cell precursor acute lymphoblastic leukemia (Ph+ BCP-ALL). (ASCO 2026) - P1 | "Olverembatinib combined with blinatumomab shows promising clinical activity in patients with R/R Ph+ BCP-ALL or CML-LBP outside China, with encouraging response rates and MRD clearance. The regimen was generally well tolerated, with a safety profile consistent with individual agent toxicities. These findings support further investigation of this chemotherapy-free approach."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Neutropenia • Pancreatitis • Thrombocytopenia • ABL1

Olverembatinib (HQP1351) Overcomes Ponatinib Resistance in Patients with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) (ASH 2022) - P1 | "A total of 21 (70.0%) patients were pretreated with third-generation TKI ponatinib, including 17 (81.0%) with resistance and 4 (19.0%) with intolerance; a total of 5 (16.7%) were pretreated with asciminib; 12 (40.0%) had T315I mutations; and 13 (43.3%), hypertension. Internal study identifier: HQP1351-CU101. Clinicaltrials.gov identifier: NCT04260022."

Clinical • Acute Lymphocytic Leukemia • Cardiovascular • Chronic Myeloid Leukemia • Hematological Malignancies • Hypertension • Neutropenia • Thrombocytopenia • ABL1 • BCR