Ascentage Pharma Releases Latest Clinical Data from Multiple Trials at ASCO 2026

Ascentage Pharma Unveils Promising Clinical Data for Three Lead Candidates at ASCO 2026

Ascentage Pharma announced the presentation of six clinical abstracts at the 2026 ASCO Annual Meeting, showcasing data from its three lead drug candidates: BCR-ABL inhibitor olverembatinib, Bcl-2 inhibitor lisaftoclax, and MDM2-p53 inhibitor alrizomadlin. The presentations included rapid oral and poster sessions, highlighting promising efficacy and manageable safety profiles across various hematologic malignancies and solid tumors. Key findings included high response rates for olverembatinib in CML and Ph+ BCP-ALL, preliminary antitumor activity for alrizomadlin in pediatric sarcomas, and efficacy of olverembatinib in SDH-deficient tumors. The company also provided updates on its global Phase 3 registrational trials, POLARIS-2 and GLORA.

• Updated data for olverembatinib as second-line therapy in CP-CML showed a 91.3% complete cytogenetic response (CCyR) rate and a 60.9% major molecular response (MMR) rate at cycle 24 among 42 evaluable patients. Additionally, in combination with blinatumomab for R/R Ph+ BCP-ALL or CML-LBP, four out of five MRD-positive patients achieved complete response, with two achieving MRD negativity, demonstrating feasibility and a manageable safety profile.
• A multicenter trial in China evaluated alrizomadlin as monotherapy or in combination with lisaftoclax in heavily pretreated pediatric patients with relapsed/metastatic rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), and other soft-tissue sarcomas (STSs). The regimen showed a manageable safety profile with no DLTs, and preliminary antitumor activity, including one complete response in monotherapy and an objective response rate of 30% and disease control rate of 80% in the combination group.
• Clinical and translational results for olverembatinib in SDH-deficient tumors revealed its efficacy in GIST and paraganglioma. Among 26 GIST patients, 23.1% achieved partial response with a median PFS of 25.7 months. For 6 paraganglioma patients, the clinical benefit rate was 66.7% with a median PFS of 8.25 months. The study also provided new insights into olverembatinib's mechanism, showing it inhibits fatty acid-promoted tumor cell migration by targeting the p38-CD36 pathway.
• Ascentage Pharma provided updates on two global Phase 3 registrational trials in progress. The POLARIS-2 trial is evaluating olverembatinib in CP-CML patients who have received at least two prior TKIs, with a primary endpoint of MMR rate at 24 weeks. The GLORA trial is assessing lisaftoclax in combination with a BTK inhibitor for previously treated CLL/SLL patients who had suboptimal response to BTKi monotherapy, aiming to enroll approximately 440 patients across 18 countries.

Olverembatinib's Promising Efficacy in CML and Ph+ BCP-ALL

Recent studies demonstrate significant advances in CML treatment strategies, spanning novel targeted therapies, treatment optimization approaches, and resistance mechanisms. These investigations provide critical insights for both first-line and salvage therapy decisions in chronic and accelerated phase disease.

• ASC4FIRST Study (2026): Evaluated asciminib 80 mg once-daily in newly diagnosed Ph+ CML-CP patients, demonstrating efficacy through BCR::ABL1 mRNA transcript time-course analysis for first-line treatment optimization

• ASCEMBL Study (2026): Investigated asciminib in third-line or later treatment for patients with at least two prior TKI failures, showing measurable efficacy outcomes based on BCR::ABL1 transcript kinetics

• ASC2ESCALATE Study (2026): Demonstrated asciminib second-line efficacy in 36 patients, with predicted major molecular response rates of 61-67% at week 48 and 70-76% at week 96 using 80 mg total daily dosing

• Italian CML Network Cohort Study (2026): Compared first-line imatinib (n=840), nilotinib (n=490), and dasatinib (n=332) in 1,662 patients, showing 2-year resistance rates of 18.3%, 6.8%, and 8.4% respectively, with dasatinib demonstrating higher intolerance rates (12.4%) versus imatinib (8.5%) and nilotinib (5.2%)

• Treatment-Free Remission Study (2025): Single-center cohort of 39 patients comparing three TKI cessation strategies achieved 63% sustained TFR at median 21-month follow-up, with equivalent outcomes (59-61%) across abrupt cessation, dose tapering, and upfront dose reduction approaches, and no disease progression events

• Olverembatinib in Accelerated-Phase CML (2025): Demonstrated efficacy in 130 subjects failing ≥1 TKIs (91 with T315I mutation), achieving 6-year cumulative incidences of 59% major cytogenetic response and 52% major molecular response, with 81% transformation-free survival and acceptable toxicity profile

POLARIS-2: A Global Registrational Trial for Olverembatinib in CML

Recent global registrational trials for CML have focused on optimizing treatment strategies through dose modifications, molecular response maintenance, and novel targeted approaches. The most significant recent studies include the ASC4FIRST phase III trial evaluating asciminib as first-line therapy and the Italian OPTkIMA study investigating TKI dose de-escalation strategies in elderly patients.

Olverembatinib's Novel Mechanism and Potential in SDH-Deficient Tumors

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) represents the primary indication for olverembatinib trials beyond chronic myeloid leukemia. Clinical investigations span multiple disease settings including newly diagnosed patients, relapsed/refractory cases, and post-transplant maintenance therapy. The largest study is a single-center, single-arm phase 2 trial (NCT05594784) that enrolled 79 patients with newly diagnosed Ph+ ALL, combining olverembatinib with venetoclax and reduced-intensity chemotherapy. This trial achieved a complete molecular response rate of 62.0% at 3 months, with estimated 1-year overall survival of 93.1% and event-free survival of 89.1%. Additional studies have demonstrated particular efficacy in patients harboring the challenging T315I mutation, with overall response rates of 71.4% in overt relapsed/refractory disease and 60.0% achieving minimal residual disease flow negativity in MRD-positive patients.

The intervention models for Ph+ ALL trials encompass diverse therapeutic approaches tailored to specific patient populations and disease stages. For newly diagnosed patients, olverembatinib is administered at 40 mg daily for 28 days combined with prednisone and vindesine as induction therapy, followed by consolidation with cytarabine and methotrexate. In the relapsed/refractory setting, olverembatinib functions as monotherapy for elderly patients or in combination with agents like inotuzumab ozogamicin for patients with resistant mutations. Post-transplant maintenance represents another key intervention model, where 26 patients received olverembatinib either prophylactically (69.2%) or preemptively (30.8%) at median doses of 35 mg every other day, resulting in a hematologic relapse rate of only 7.7% and 3-year overall survival of 91.7%.

Preclinical investigations have extended olverembatinib's potential therapeutic scope to solid tumors, particularly endometrial cancer. Laboratory studies across seven endometrial cancer cell lines demonstrated significant antiproliferative effects, with cancer cells showing greater sensitivity compared to normal cells (p = 0.030). The compound significantly inhibited migration in both endometrioid (Ishikawa) and serous (ARK1) cell lines while reducing invasion in ARK1 cells. RNA sequencing analysis revealed modulation of key oncogenic pathways including ROR1/Wnt, GCN2-ATF4, epithelial-to-mesenchymal transition, and PI3K-AKT signaling. These findings support further clinical investigation of olverembatinib in endometrial cancer, potentially in combination with immune checkpoint inhibitors, though no clinical trials have yet been initiated in this indication.

Ascentage Pharma's Multi-Modal Strategy Targets Resistant Cancers

Ascentage Pharma's recent ASCO presentations paint a compelling picture of a company strategically advancing a diverse pipeline of targeted therapies, particularly in areas marked by significant unmet needs and drug resistance. The spotlight on olverembatinib, a third-generation BCR-ABL inhibitor, reinforces its critical role in overcoming the challenging T315I mutation and broader TKI resistance in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). With promising data in both adult and pediatric populations, and its inclusion in updated CML guidelines, olverembatinib is poised to become a cornerstone therapy. However, the literature suggests that, like some other potent TKIs, olverembatinib may be associated with cardiovascular toxicities, necessitating careful patient selection and dose optimization strategies, such as the 30 mg every other day regimen, to balance efficacy with tolerability. The ongoing POLARIS-2 and GLORA Phase 3 trials will be crucial in solidifying its global market position and exploring its potential in SDH-deficient tumors.

Meanwhile, lisaftoclax, a selective Bcl-2 inhibitor, is carving out a niche, particularly with its demonstrated activity in chronic lymphocytic leukemia (CLL) patients previously exposed to venetoclax. This positions it as a valuable option for patients who have exhausted other Bcl-2 inhibitor treatments, offering a new pathway for disease control. While Bcl-2 inhibitors are known for risks like neutropenia and thrombocytopenia, the observed manageable safety profile with dose ramp-up is encouraging. The synergistic potential of lisaftoclax in combination with other agents, such as homoharringtonine in acute myeloid leukemia (AML), further highlights its versatility.

Finally, alrizomadlin, an MDM2-p53 inhibitor, represents a distinct approach by restoring the tumor suppressor function of p53 in wild-type tumors. Its preliminary antitumor activity in pediatric sarcomas and other solid tumors, especially those with MDM2 amplification, addresses a critical need for novel mechanisms in these difficult-to-treat cancers. However, its efficacy is contingent on the patient's TP53 wild-type status, and clinicians must be prepared to manage significant hematologic toxicities, including thrombocytopenia and neutropenia, which are common with this class of agents. Ascentage's strategic focus on these three distinct mechanisms underscores a commitment to precision oncology, aiming to provide effective solutions for patient populations facing limited therapeutic options.