Nailike (olverembatinib)

P1, N=48, Not yet recruiting, Ascentage Pharma Group Inc.

Non-cytotoxic concentrations of olverembatinib significantly increased the sensitivity of ABCB1-overexpressing cells to paclitaxel and vincristine. Additionally, olverembatinib activated the ATPase activity of ABCB1 in a concentration-dependent manner and exhibited potent binding affinity to ABCB1 in docking simulations. These findings suggest that olverembatinib holds promise as a potent reversal agent for MDR, paving the way for its integration into novel combination chemotherapy regimens to improve cancer treatment outcomes.

The treatment safety of the entire process was excellent. In summary, olverembatinib provides more treatment options for rare diseases such as 8p11 myeloproliferative syndrome.

She ultimately achieved Major Molecular Response (MMR) after haploidentical hematopoietic stem-cell transplantation (haplo-HSCT). This case highlights the importance of comprehensive molecular profiling at diagnosis and the need to develop alternative therapeutic strategies for rare BCR::ABL1 variants.

3G-TKI with azacitidine is an effective and safe therapy providing more chance to receive a transplantation for CML in myeloid blast phase. Potential biomarkers associated with outcomes were identified.

P1, N=242, Recruiting, Ascentage Pharma Group Inc. | N=62 --> 242 | Trial completion date: Jan 2024 --> Mar 2030 | Trial primary completion date: Jan 2024 --> Dec 2029

Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) are generally resistant to targeted therapy with tyrosine kinase inhibitors (TKIs), such as imatinib, and there are no standard therapeutic options for advanced SDH-deficient GISTs. As a putative mechanism of action, translational research revealed significant lipid enrichment with the overexpression of lipid uptake-related genes and proteins, including CD36, fatty acid binding proteins, fatty acid transport proteins, and lipid metabolites, in SDH-deficient GIST patients, and olverembatinib suppressed lipid uptake and CD36 expression in GIST cells. Olverembatinib also exerts antitumor effects by inhibiting tumorigenic signaling pathways associated with hypoxia, angiogenesis, proliferation, and survival.

There were acceptable treatment-related adverse events. We conclude olverembatinib is effective and tolerable in subjects in accelerated phase CML failing prior TKI therapy.

Combination therapies with ponatinib or other agents, as well as newer TKIs like olverembatinib, have demonstrated potential in overcoming resistance in preclinical and clinical models. Understanding these diverse resistance mechanisms is critical for optimizing asciminib-based treatment strategies and guiding the development of effective combination therapies for patients with resistant CML.

P1/2, N=458, Recruiting, Ascentage Pharma Group Inc. | N=284 --> 458 | Trial completion date: Aug 2026 --> Sep 2029 | Trial primary completion date: Aug 2025 --> Sep 2028

P2, N=60, Not yet recruiting, M.D. Anderson Cancer Center

P3, N=150, Recruiting, Institute of Hematology & Blood Diseases Hospital, China