On November 5, 2021 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that abstracts on three clinical trials of the company’s novel drug candidate, olverembatinib (HQP1351), have been selected for poster presentations and one oral presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Ascentage Pharma, NOV 5, 2021, View Source;ascentage-pharma-to-present-three-studies-of-olverembatinib-hqp1351-a-novel-drug-candidate-for-the-treatment-of-drug-resistant-leukemia-in-abstracts-including-one-oral-report-at-ash-annual-meeting-301417333.html [SID1234594615]). Presenter, Qian Jiang, MD, and Xiaojun Huang, MD, from the Hematology Department of Peking University People’s Hospital are the principal investigators of the study selected for oral presentation. This is the fourth consecutive year in which studies of olverembatinib were selected for oral presentation by the ASH (Free ASH Whitepaper) Annual Meeting, demonstrating strong recognition of the drug candidate’s promising efficacy and safety by the international hematology community.
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Olverembatinib is a novel third-generation BCR-ABL tyrosine kinase inhibitor (TKI) developed by Ascentage Pharma for the treatment of patients with chronic myeloid leukemia (CML) resistant to first- and second-generation TKIs, including those with the T315I mutation, which confers resistance against these agents. The New Drug Application (NDA) submitted by Ascentage Pharma for olverembatinib for the treatment of patients with T315I-mutated CML in chronic-phase (CML-CP) or accelerated-phase (CML-AP) is currently under review in China and has already been granted the Priority Review status. Moreover, olverembatinib was granted a Breakthrough Therapy designation by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) for the treatment of patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs.
The ASH (Free ASH Whitepaper) Annual Meeting is one of the largest gatherings of the international hematology field, bringing together the latest and most cutting-edge research and other scientific and clinical developments in hematology. The 63rd ASH (Free ASH Whitepaper) Annual Meeting will take place on December 11-14, 2021, both virtually and in-person in Atlanta, Georgia, United States. This year, six abstracts on three of Ascentage Pharma’s drug candidates (olverembatinib, lisaftoclax [APG-2575], and pelcitoclax [APG-1252]) have been selected by the ASH (Free ASH Whitepaper) Annual Meeting for poster or oral presentations (information on those abstracts about lisaftoclax [APG-2575] and pelcitoclax [APG-1252] are available in a separate press release published in parallel).
Drug Candidate
Abstract Title
Abstract#
Format
Olverembatinib
(HQP1351)
Updated Safety and Efficacy Results of Phase 1 Study of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic Myeloid Leukemia (CML)
311
Presentation
Updated Results of Pivotal Phase 2 Trials of Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant BCR-ABL1T315I-Mutated Chronic- and Accelerated-Phase Chronic Myeloid Leukemia (CML-CP and CML-AP)
3598
Poster Presentation
Trial in Progress: Phase 1b Bridging Study of the Pharmacokinetic (PK), Safety, and Efficacy of Orally Administered Olverembatinib (HQP1351) in Patients with Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
2551
Poster Presentation
Lisaftoclax (APG-2575)
A Phase 1 Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor (BCL-2i), in Patients (pts) with Certain Relapsed or Refractory (R/R) Hematologic Malignancies (HMs)
3730
Poster Presentation
Trial in Progress: Phase 1b Study of Lisaftoclax (APG-2575) As a Single Agent or Combined with Other Therapeutic Agents in Patients with Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (R/R CLL/SLL)
1554
Poster Presentation
Pelcitoclax (APG-1252)
Antitumor Activity of Dual BCL-2/BCL-xl Inhibitor Pelcitoclax (APG-1252) in Natural Killer/T-Cell Lymphoma (NK/TCL)
2062
Poster Presentation
"These data to be reported at the 2021 ASH (Free ASH Whitepaper) Annual Meeting are very encouraging as they demonstrated olverembatinib’s promising efficacy and tolerability profiles. This is the fourth year in which the clinical progress of this drug candidate has been selected for oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting, a strong indication of the international hematology community’s recognition of olverembatinib’s potential as a new treatment option for patients with CML," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As China’s first and the world’s second third-generation BCR-ABL inhibitor, olverembatinib offers patients with CML a potential new treatment with clear efficacy and potentially enhanced safety. We hope that olverembatinib will soon be granted market authorization so that patients with CML in China and around the world can start benefiting from this novel therapeutic."
These abstracts selected for presentations at 2021 ASH (Free ASH Whitepaper) Annual Meeting are as follows:
Updated Safety and Efficacy Results of Phase 1 Study of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic Myeloid Leukemia (CML)
Format: Oral Presentation
Abstract: 311
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Mechanisms of resistance and expanded therapies
Time: Saturday, December 11, 2021; 5:00 PM EDT
Highlights
– This Chinese, open-label, multicenter, Phase I trial evaluated the safety and efficacy of olverembatinib in adults with CML-CP or CML-AP. Eligible patients had CML-CP or CML-AP resistant or intolerant to first- and second-generation TKIs. Olverembatinib was orally administered once every other day (QOD) in 28-day cycles and at 11 dose cohorts ranging from 1 to 60 mg. This study reports data on patients with long-term follow-up.
– From October 26, 2016, through February 2, 2021 (data cut-off date), 101 patients with CML-CP (n=86) or CML-AP (n=15) were enrolled and treated with olverembatinib. A total of 71 (70.3%) patients were male, the median age was 40 (range, 20-64) years, and the median (range) interval from diagnosis to initial olverembatinib treatment was 6.0 (0.3-15.2) years. In all, 84 (83.2%) patients received ≥ 2 prior lines of TKI-therapies, and 63 (62.4%) harbored the T315I mutation. At baseline, compound mutations were detected in 11 (10.9%) patients, of whom 7 (63.6%) had the BCR-ABL1T315I genotype. A total of 20 (19.8%) patients had 2 (n=13) or ≥ 3 (n=7) mutations. The median follow-up was 30.8 (1.2-51.8) months. As of the data cutoff date, 81 (80.2%) of 101 patients continued on the treatment, 18 (17.8%) were treated for > 3 years, and 5 (5%) for > 4 years.
– Of evaluable patients without baseline responses, 97.0% had complete hematologic responses (CHR), 62.1% had complete cytogenetic responses (CCyR), and 51.0% had major molecular responses (MMR).
– Among patients in CML-CP, most evaluable patients with T315I mutations experienced CHR (100%), MCyR (83.7%), or MMR (71.2%).
– Among patients in CML-AP, 80.0% experienced CHR and 54.5% each MCyR or MMR.
At 36 months, the progression-free survival (PFS) rate was 96.3% (89.1%-98.8%) in patients with CML-CP and 71.4% (40.6%‒88.2%) in those with CML-AP.
Treatment responses were durable and unaffected by baseline BCR-ABL1 mutational status. Corresponding values in patients with> 4 years of treatment were 100% (CHR), 80% (CCyR), and 60% (MMR). The mean PFS rate was 100% at 36 or 48 months and not reached (NR-NR) at 60 months.
– Most treatment-related adverse events (TRAEs) were grade 1 or 2.
– The most frequent nonhematologic adverse event (AE) was (mostly grade 1 or 2) skin hyperpigmentation (86.1%). Grade ≥ 3 nonhematologic AEs included hypertriglyceridemia (10.9%), pyrexia (6.9%), and proteinuria (5.0%).
– The most common hematologic TRAE was thrombocytopenia in 78 (77.2%) patients, including 52 (51.5% of total population) with grade ≥ 3. Leukopenia was grade ≥ 3 in 21 (20.8%) patients but not serious, while anemia was grade ≥ 3 in 16 (15.8%) patients.
– Conclusions: In patients with TKI-resistant CML-CP or CML-AP and long-term treatment, olverembatinib was efficacious and well tolerated.
Updated Results of Pivotal Phase 2 Trials of Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant BCR-ABL1T315I-Mutated Chronic- and Accelerated-Phase Chronic Myeloid Leukemia (CML-CP and CML-AP)
Format: Poster Presentation
Abstract: 3598
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster III
Time: Monday, December 13, 2021; 6:00 PM – 8:00 PM EDT
Highlights:
– HQP1351-CC201 and HQP1351-CC202 are Chinese open, single-arm, multicenter pivotal Phase II trials evaluating the safety and efficacy of olverembatinib in adults with TKI-resistant (BCR-ABL1T315I-mutated) CML-CP and CML-CP, respectively. Olverembatinib was administered at 40 mg orally QOD for 28-day cycles.
– As of the data cutoff of August 25, 2020, HQP1351-CC201 had enrolled 41 patients with CML-CP, of whom 32 (78%) completed ≥ 12 cycles. The median follow-up was 13 (3.1-16.3) months. After ≥ 12 treatment cycles in patients without responses at baseline, all 31 (100%) experienced CHR (10 other patients had CHR at baseline); 31/41 (75.6%) MCyR; 28/41 (68.3%) CCyR; and 23/41 (56.1%) MMR. At 12 months, the PFS rate was 89.3%, and overall survival (OS) 100%.
– As of the data cutoff of July 27, 2020, HQP1351-CC202 had enrolled 23 patients with CML-CP, of whom 14 (61%) had completed≥ 12 cycles. The median (range) follow-up was 13.5 (1.4-15.2) months. After ≥ 12 treatment cycles in patients without responses at baseline, 17/23 (73.9%) experienced MaHR; 12/23 (52.2%) MCyR; 11/23 (47.8%) CCyR; and 9/23 (39.1%) MMR. At 12 months, the PFS rate was 74.1%, and the OS 91.3%.
– In HQP1351-CC201, the most frequent grade 3-4 TRAE was thrombocytopenia (48.8%), and no treatment-related deaths occurred.
– In HQP1351-CC202, the most frequent grade 3-4 TRAE was thrombocytopenia (56.5%).
– Conclusions: Olverembatinib was efficacious and well tolerated when administered as monotherapy in patients with TKI-resistant CML-CP or CML-AP and the BCR-ABL1T315I mutation.
Trial in Progress: Phase 1b Bridging Study of the Pharmacokinetic (PK), Safety, and Efficacy of Orally Administered Olverembatinib (HQP1351) in Patients with Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Format: Poster Presentation
Abstract: 2551
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II
Time: Sunday, December 12, 2021; 6:00 PM – 8:00 PM EDT
Highlights:
– This open-label bridging trial in the US is evaluating the PK, efficacy, and safety of olverembatinib administered orally QOD in adults who have CML-CP, CML-AP or blast-phase CML (CML-BP) and Ph+ ALL.
– This study is currently recruiting patients, with enrolled individuals being allocated to three dose cohorts: 30, 40, or 50 mg QOD orally. Endpoints of this study include PK, antitumor activity, and safety.