Ascentage Pharma Presents Data on Olverembatinib in CML-LBP and Ph+ BCP-ALL at ASCO 2026

Ascentage Pharma Presents Encouraging Phase Ib Data for Olverembatinib Combo at ASCO 2026

Ascentage Pharma announced encouraging results from a Phase Ib study evaluating olverembatinib in combination with blinatumomab for patients with lymphoid blast phase chronic myeloid leukemia (CML-LBP) or Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ BCP-ALL). Presented at the 2026 ASCO Annual Meeting, this marks the first international disclosure of the combination. The regimen demonstrated strong clinical activity, including high rates of complete response (91%) and minimal residual disease (MRD) clearance (80%), alongside a generally well-tolerated safety profile consistent with individual agents. These findings highlight its potential as a novel, chemotherapy-free strategy for these difficult-to-treat hematologic malignancies.

• The Phase Ib study showcased significant efficacy, with 91% (10/11) of patients achieving complete response (CR) or complete response with incomplete hematologic recovery (CRi). Additionally, deep molecular responses were observed, with 67% (8/12) achieving BCR::ABL1 negativity by PCR (≤0.01%) and 80% (8/10) achieving minimal residual disease (MRD) negativity by flow cytometry (≤0.01%) in this challenging patient population.
• The combination regimen of olverembatinib and blinatumomab demonstrated a manageable safety profile. Most adverse events (AEs) reported were mild, classified as Grade 1-2, and were consistent with the known toxicities of each agent when administered individually. This suggests that the combination therapy does not introduce unexpected or severe safety concerns, supporting its potential for broader clinical application.
• This rapid oral presentation at ASCO 2026 represents the first international validation of olverembatinib combined with immunotherapy for CML-LBP and relapsed/refractory Ph+ BCP-ALL. These diseases are recognized as among the most difficult-to-treat BCR-ABL-driven hematologic malignancies, often associated with terminal stages, poor prognoses, and limited treatment options, underscoring the potential of this novel, chemotherapy-free therapeutic approach.

Addressing Unmet Needs in CML-LBP and Ph+ BCP-ALL

Lymphoid blast crisis represents a critical unmet medical need in chronic myeloid leukemia, with patients experiencing an average overall survival of less than one year despite current therapeutic advances. Tyrosine kinase inhibitors demonstrate significantly reduced efficacy in blast crisis compared to chronic phase CML, where survival rates approach those of the general population.

• Treatment-free remission failures - Nine out of eleven reported blast crisis cases during TFR presented as lymphoid blast crisis, with additional gene mutations frequently observed including SETD2 frameshift mutations in patients who experienced sudden transformation after 21 months in TFR without prior molecular loss

• Long-term monitoring strategies - Implementation of extended surveillance protocols following TKI discontinuation is essential due to potential late-onset blast crisis, with systematic genetic studies needed to understand mechanisms and develop predictive biomarkers

• Early disease progression detection - No universal molecular biomarkers currently exist to identify CML patients at risk of blast crisis transformation, limiting ability to implement timely therapeutic interventions to delay or prevent progression

• Advanced phase treatment optimization - Patients diagnosed in blast crisis show significantly higher likelihood of not achieving complete/partial hematologic response, emphasizing the need for transplantation before disease progression and improved treatment protocols for advanced disease

• Novel therapeutic targets - Recent research has identified PABPC1 as a driver of blast crisis progression and ARDAP derivatives as potential tubulin inhibitors that may overcome broad TKI resistance in relapsed/refractory patients

• Genetic assessment integration - Earlier recognition of end-phase disease through comprehensive genetic evaluation may improve clinical outcomes, particularly for patients with T315I mutations requiring third-generation TKIs or alternative therapeutic approaches

Olverembatinib's Expanding Pipeline in Hematologic Malignancies

Olverembatinib and blinatumomab are being investigated across multiple hematologic malignancies beyond lymphoid blast phase chronic myeloid leukemia. Both agents demonstrate broad therapeutic potential in various phases of leukemia and lymphoma, with distinct intervention models tailored to their mechanisms of action.

Paving a Chemotherapy-Free Path in Advanced Ph+ Leukemias

The recent disclosure of positive Phase Ib data for Ascentage Pharma's olverembatinib in combination with blinatumomab marks a potentially transformative moment for patients battling lymphoid blast phase chronic myeloid leukemia (CML-LBP) and Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ BCP-ALL). These are aggressive forms of leukemia where treatment options are often limited, and prognoses remain poor. While tyrosine kinase inhibitors (TKIs) have significantly improved outcomes in CML, the emergence of resistance, particularly due to specific BCR-ABL1 mutations like T315I, continues to pose a substantial clinical hurdle. Olverembatinib, a third-generation TKI, has already demonstrated robust activity against such resistant mutations.

The strategic combination with blinatumomab, an established immunotherapy, offers a compelling chemotherapy-free strategy. This approach is highly attractive, as it aims to circumvent the severe toxicities and complications associated with conventional intensive chemotherapy regimens, which can significantly impact a patient's quality of life and long-term health. The reported high rates of complete response and minimal residual disease (MRD) clearance are particularly encouraging, as deep molecular responses are strongly associated with improved long-term survival and the potential for eventual treatment-free remission.

However, it is crucial to consider that these are early-phase results. While promising, the findings from a Phase Ib study, typically involving a small patient cohort, require validation in larger, later-phase clinical trials to definitively establish efficacy and long-term safety. The long-term safety profile of this combination, including potential cumulative toxicities or novel adverse events, will need careful monitoring, as patient adherence to TKI therapy is paramount for successful outcomes. Furthermore, despite the potency of olverembatinib against known resistance mutations, the inherent adaptability of advanced leukemias means that the emergence of new BCR-ABL1 mutations or BCR-ABL1-independent resistance mechanisms remains a persistent risk that could challenge long-term disease control. Nevertheless, this combination represents a significant step forward, offering a targeted, less toxic, and highly effective potential new standard for these challenging hematologic malignancies.