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1798 Update of Olverembatinib (HQP1351) Overcoming Ponatinib and/or Asciminib Resistance in Patients (Pts) with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Elias Jabbour1, Hagop M. Kantarjian, MD2, Paul B. Koller, MD3, Omer Jamy, MD4, Vivian G. Oehler5*, Elza Lomaia6*, Anthony M. Hunter, MD7*, Olga Uspenskaya8*, Svetlana Samarina9*, Sudipto Mukherjee, MD, PhD, MPH10, Maria R. Baer, MD11, Vera Zherebtsova12*, Vasily Shuvaev13*, Anna Turkina, MD14*, Igor Davydkin15*, Jorge Cortes, MD16, Huanshan Guo17*, Zi Chen18*, Lei Fu19*, Hengbang Wang18*, Lixin Jiang19*, Cunlin Wang19*, Dajun Yang18,19,20* and Yifan Zhai17,18,19

1University of Texas M.D. Anderson Cancer Ctr., Houston, TX
2Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
3Hematology/HCT, City of Hope National Medical Center, Duarte, CA
4Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
5Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
6FSBI “National Medical Research Center named after V.A. Almazov” of the MOH of Russia, Saint-Petersburg, Russian Federation
7Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta
8Leningrad Regional Clinical Hospital, Saint-Petersburg, Russian Federation
9FGBUN “Kirov Scientific Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency”, Kirov, Russian Federation
10Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
11Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
12S.P. Botkin City Clinical Hospital, Moscow, Russian Federation
13Russian Research Institute of Hematology and Transfusiology, Saint-Petersburg, Russian Federation
14National Medical Research Center for Hematology, Moscow, Russian Federation
15Federal State Budgetary Educational Institution of Higher Education “Samara State Medical University” of the Ministry of Healthcare of the Russian Federation, Samara, Russian Federation
16Georgia Cancer Center, Augusta University, Augusta, GA
17Guangzhou Healthquest Pharma Co., Ltd., Guangzhou, China
18Ascentage Pharma (Suzhou) Co., Ltd., Suzhou, China
19Ascentage Pharma Group Inc., Rockville, MD
20Department of Experimental Research, State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China


Olverembatinib, a novel, potent BCR::ABL1 tyrosine kinase inhibitor (TKI), shows strong antitumor activity in pts with CML and Ph+ ALL. Here, we report on the safety, efficacy, and pharmacokinetic (PK) profiles of olverembatinib in pts with CML (all phases) and Ph+ ALL outside of China, particularly in pts previously treated with ponatinib and/or asciminib.


Olverembatinib was administered orally once every other day (QOD) in continuous 28-day cycles. In the monotherapy cohort, pts were enrolled after treatment failure on at least 2 prior TKIs and randomized to olverembatinib QOD 30, 40, or 50 mg. In the combination cohort, pts with Ph+ B-cell precursor (BCP) ALL or lymphoid CML-BP (CML-LBP) resistant to at least 1 TKI were enrolled and received olverembatinib (30 or 40 mg) QOD in combination with blinatumomab.


As of June 30, 2023, 76 pts were enrolled, including 57 with CML-CP and 19 with advanced Ph+ leukemia. The median (range) age was 54.5 (21-80) years, and 56.6% of pts were male. In all, 11 (14.5%), 23 (30.3%), and 39 (51.3%) pts had received 2, 3, and ≥ 4 prior TKIs, respectively. A total of 52.6% of pts were previously treated with ponatinib, of whom 67.5% were resistant and 25.0% intolerant to the drug, and 7.5% experienced treatment failure for other reasons. A total of 27.6% of pts were previously treated with asciminib, of whom 71.4% were resistant and 19.1% intolerant to the agent, and 9.5% experienced treatment failure for other reasons. At baseline, 32% of pts had T315I mutations, 38% hypertension, and 17.1% other cardiovascular comorbidities. Median (range) treatment duration was 24.1 (0-134) weeks, and PK profiles were similar to historical PK data on Chinese pts. Twelve pts with CML-CP and 7 with advanced Ph+ leukemia discontinued treatment: 4 because of AEs, 7 disease progression, and 8 other reasons. A total of 54 of 65 (83.1%) pts who received ≥ 1 dose of olverembatinib experienced any-grade TRAEs. Grade ≥ 3 AEs occurring in ≥ 3 pts (≥ 4.6% incidence) included thrombocytopenia (17%); neutropenia (13.8%); elevated blood creatine phosphokinase (13.8%); leukopenia (7.7%); and anemia and elevated lipase (4.6% each). Ten (15.4%) pts experienced olverembatinib treatment-related serious AEs, of which each were experienced by 1 (1.5%) pt. Two (3.1%) pts discontinued the study because of TRAEs. No TRAE-associated deaths were reported. Olverembatinib showed sustained antileukemic activity in pts with CML and Ph+ ALL (Table 1). Among 50 efficacy-evaluable pts with CML-CP, the rate of complete cytogenetic response (CCyR) was 57% (25/44) and major molecular response (MMR) 43% (21/49). Efficacy improved over time; the MMR rate in pts with CML-CP treated for 6 months was 66% and 88% in pts treated for 12 months. Among pts whose disease failed ≥ 4 prior TKIs, CCyR and MMR rates were 57% (13/23) and 42% (11/26), respectively. In pts with CML-CP harboring the T315I mutation, rates of CCyR and MMR were 60% (9/15) and 44% (7/16), respectively, and 55% (16/29) and 42% (14/33) in pts without the T315I mutation. Among evaluable ponatinib-failed pts, 8/15 (53%) achieved CCyR and 6/16 (38%) MMR. Among pts who failed asciminib therapy, 3/7 (43%) achieved CCyR and 3/8 (38%) MMR. Of 8 pts with CML-CP who had prior exposure to both ponatinib and asciminib, 2 (25%) achieved MMR. At 24 months, PFS was 75% (95% CI, 56.1-86.7) and OS was 97.6% (95% CI, 90.8-99.4). Thirteen pts with advanced Ph+ leukemia were efficacy-evaluable, of whom 3 (23%) achieved MMR; only 1 of 3 pts with the T315I mutation achieved MMR; the other 2 were also resistant to ponatinib treatment. The median (95% CI) PFS of efficacy-evaluable pts with advanced leukemia was 12.7 (4-19.5) months. In the combination cohort, 2 pts with Ph+ BCP ALL received olverembatinib 30 mg QOD with blinatumomab; both achieved CCyR and 1 achieved a negative MRD status after 1 treatment cycle.


Olverembatinib alone or combined with blinatumomab was efficacious and well tolerated in pts with heavily pretreated CML or Ph+ ALL. Olverembatinib monotherapy was potent in pts who were either resistant or intolerant to ponatinib and/or asciminib, regardless of T315I mutation status. Olverembatinib may provide an effective new treatment option for pts after failure of 2 or more TKIs. Internal study identifier: HQP1351-CU101. Clinicaltrials.gov identifier: NCT04260022.

Disclosures: Jabbour: Hikma Pharmaceuticals: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Ascentage Pharma Group: Consultancy, Honoraria, Research Funding; Adaptive Biotech: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Astex: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding. Kantarjian: Shenzhen Target Rx: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Labcorp: Honoraria, Research Funding; KAHR medical: Honoraria, Research Funding; Ipsen Biopharmaceuticals: Honoraria, Research Funding; Curis: Honoraria, Research Funding; Biologix: Honoraria, Research Funding; Astellas: Honoraria, Research Funding; Ascentage: Honoraria, Research Funding; Amphista: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Stemline: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Daiichi-Sankyo: Research Funding; Immunogen: Research Funding; Jazz: Research Funding. Koller: takeda: Consultancy, Speakers Bureau; NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; treadwell therapuetics: Consultancy, Other: safety review committee. Jamy: Ascentage: Other: Advisory Board Participation. Hunter: Sierra Oncology: Membership on an entity's Board of Directors or advisory committees. Mukherjee: Bristol Myers Squibb: Consultancy; Bristol Myers Squibb: Other: Advisory Board; Aplastic Anemia and MDS International Foundation: Honoraria; EUSA: Other: Advisory Board; McGraw Hill Hematology Oncology Board Review: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Consultancy; Celgene (now BMS): Honoraria; Celgene (now BMS): Consultancy; Celgene/Acceleron: Other: Advisory Board; Novartis: Other: Advisory Board; Blueprint Medicines Corporation: Other: Advisory Board; Genentech and AbbVie: Other: Advisory Board; EUSA: Honoraria; BioPharm: Consultancy; Celgene (now BMS): Research Funding; Novartis: Research Funding; Jazz Pharmaceuticals: Research Funding. Baer: Takeda (Inst): Research Funding; Abbvie (Inst): Research Funding; Ascentage Pharma (Inst): Research Funding; FORMA Therapeutics (Inst): Research Funding; Kite, a Gilead company (Inst): Research Funding; Kura Oncology (Inst): Research Funding. Turkina: Fusion Pharma: Speakers Bureau; Pfizer: Other: Travel, accommodation expenses, Speakers Bureau; Novartis: Other: Travel, accommodation expenses, Speakers Bureau. Cortes: Biopath Holdings: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Research Funding; Gilead: Consultancy; Abbvie: Consultancy, Research Funding; Forma Therapuetic: Consultancy; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Research Funding. Guo: Ascentage Pharma: Current Employment, Current equity holder in publicly-traded company. Chen: Ascentage Pharma: Current Employment, Current equity holder in publicly-traded company. Fu: Ascentage Pharma: Current Employment, Current holder of stock options in a privately-held company. Wang: Ascentage Pharma: Current Employment, Current equity holder in publicly-traded company. Jiang: Ascentage Pharma: Current Employment, Current holder of stock options in a privately-held company. Wang: Ascentage Pharma: Current Employment, Current equity holder in publicly-traded company. Yang: Ascentage Pharma: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership, Patents & Royalties. Zhai: Ascentage Pharma: Current Employment, Current equity holder in publicly-traded company, Other: Leadership (CMO).

*signifies non-member of ASH