Nailike (olverembatinib)

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

She presented with a complex karyotype and showed good early response to imatinib and dasatinib but relapsed six months after diagnosis, and E255v, T315I mutations were successively detected in the ABL kinase region, then he switched to ponatinib and underwent allogeneic hematopoietic stem cell transplantation. But the Minimal Residual Disease increased after 16 months, the patient was treated with CD19 chimeric antigen receptor T cell immunotherapy, and changed to olverembatinib targeted therapy. This subgroup of acute lymphoblastic leukemia might have poorer prognosis than patients with common transcripts. we recommend the third-generation tyrosine-kinase inhibitor as a first choice for their initial therapy and allogeneic hematopoietic stem cell transplantation or immunotherapy and new clinical trials should be considered as early as possible.

P2, N=50, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Jul 2025 --> Jul 2026

P=N/A, N=34, Not yet recruiting, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine