ASH2024|Oral Report on Olverembatinib in Non-T315I-Mutant CP-CML

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from the ASH Annual Meeting ↑↑↑

The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, results from multiple clinical and preclinical studies on four of Ascentage Pharma’s drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at this year’s ASH Annual Meeting. Furthermore, this is the seventh consecutive year for studies of olverembatinib to be selected for Oral Reports at the meeting.

Results released through the Oral Report are the first batch of data of olverembatinib as a second-line therapy in patients with non-T315I-mutant CP-CML, which indicated that the drug may offer a safe and effective second-line therapy to patients with CP-CML, especially those who had failed on second-generation TKIs in the first-line setting. These data showed that, in patients with CP-CML who were resistant/intolerant to one prior line of TKIs, olverembatinib demonstrated a complete cytogenetic response (CCyR) rate of 74.1%, a major molecular response (MMR) rate of 40.6%; and in patients who had been treated with second-generation TKIs in the first-line setting, olverembatinib demonstrated a CCyR rate of 78.9% and an MMR rate of 43.5%, with efficacy improved over time. In terms of safety, olverembatinib showed a profile similar to that was previously reported. The study did not observe any new safety signals or report any arterial occlusive events (AOEs) or venous thromboembolisms (VTEs).

Prof. Weiming Li, of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, was orally reporting clinical results at the ASH Annual Meeting

As the first approved third-generation BCR-ABL inhibitor in China, olverembatinib has already been approved for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant CP-CML or accelerated-phase (AP-) CML harboring the T315I mutation; and adult patients with CP-CML resistant to and/or intolerant of first- and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

Olverembatinib as Second-Line (2L) Therapy in Patients (pts) with Chronic Phase-Chronic Myeloid Leukemia (CP-CML)

Format: Oral Presentation

Abstract#: 480

Session: 632. Chronic Myeloid Leukemia: Novel Molecules in Clinical Practice

Highlights:

Background: Olverembatinib, a third-generation tyrosine kinase inhibitor (TKI), has demonstrated remarkable efficacy and a favorable safety profile in patients with CML resistant and/or intolerant to at least 2 TKIs or with the T315I mutation. The aim of this study was to assess the efficacy and safety of olverembatinib as a second-line treatment for patients with CP-CML without the T315I mutation.

Introduction: This is a single-arm, multicenter, open-label study designed to evaluate the efficacy, safety, and patients’ quality of life of orally administered olverembatinib (40 mg QOD) in patients with CP-CML who were resistant/intolerant to one prior line of TKIs (including imatinib, flumatinib, nilotinib, and dasatinib) without the T315I mutation.

Enrolled Patients and Study Methods: As of November 15, 2024, the study enrolled a total of 43 patients with non–T315I-mutant CML-CP. These patients received orally administered olverembatinib 40 mg every other day (QOD) in 28-day cycles.

Efficacy Results:

• As of November 15, 2024, 33 (78.6%) patients had at least one efficacy assessment, 28 (66.7%) had at least two, 23 (54.8%) had at least three. Three patients had not yet undergone their first efficacy assessment.

• At data cutoff, 74.1% (20/27) of patients achieved a complete cytogenetic response (CCyR) and 40.6% (13/32) achieved a major molecular response (MMR). The CCyR and MMR rates evaluated at the end of Cycles 6, 9, 12, and 18 were 45.5% and 28.7%, 57.2% and 32.0%, 61.1% and 32.0%, and 68.9% and 40.7%, respectively, suggesting that efficacy improved over time.

• In 33 efficacy-evaluable patients, 24 were pretreated with second-generation TKIs as first-line treatment, of whom 78.9% (15/19) achieved CCyR, and 43.5% (10/23) achieved MMR. In 9 patients who were pretreated with imatinib, 50.0% achieved CCyR (4/8) and 33.3% achieved MMR (3/9).

Safety Results: The median (range) treatment duration was 16.0 (2-18) months. A total of 41 (95.3%) patients experienced any-grade treatment-related adverse events (TRAEs), of whom 21 (48.8%) had grade ≥ 3 treatment-related adverse events (TRAEs) and 6 (14.0%) had olverembatinib-related serious AEs (SAEs). Nonhematologic TRAEs included skin hyperpigmentation (51.2%), hyperuricemia (30.2%), and creatine phosphokinase increased (25.6%). Most of these TRAEs were grade 1 or 2. Grade ≥ 3 hematologic toxicities included platelet count decreased (46.5%), neutropenia (25.6%), and anemia (9.3%). Only one patient experience grade 1 hypertension that was possibly olverembatinib-related, and no AOEs or VTEs were reported during the study. Olverembatinib-related SAEs included platelet count decreased (7.0%), anemia and elevated ALT (2.3% each). No deaths were reported.

Conclusions: Olverembatinib may provide an effective and safe second-line treatment option for patients with CP-CML, especially those who have failed on second-generation TKIs in the first-line setting.

* Olverembatinib is an investigational drug that has not been approved for any indication outside China.

Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK.

The company has built a rich pipeline of innovative drug candidates that includes novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 13 registrational studies (completed/ ongoing/planned).

Olverembatinib, the company’s first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company’s first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU.

To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company’s investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan.

The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development.