Iclusig (ponatinib)

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Nov 2025 --> Nov 2026

Ponatinib has been successfully integrated into various treatment regimens, including both low- and high-intensity chemotherapy regimens, and in combination with blinatumomab, for adult patients with newly diagnosed Ph+ ALL. Herein, we summarize landmark trials, specifically their efficacy and toxicity profile, that established ponatinib as a standard of care for patients with newly diagnosed Ph+ ALL who are suitable medically for it.

P2, N=90, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: Nov 2025 --> Nov 2027

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.

P2, N=33, Not yet recruiting, University of Washington

TKIs, including flumatinib, may cause AKI; however, FAERS-based disproportionality analysis does not indicate an increased renal safety signal compared to non-TKIs. Among TKIs, dasatinib and nilotinib have lower reporting disproportionality than imatinib does, suggesting a potential therapeutic advantage of their use for patients with kidney diseases.

We evaluated their effects on resistance to five TKIs (imatinib, nilotinib, bosutinib, ponatinib and asciminib), spanning all four TKI generations by using K562 cells. We identified 361 pairs of resistance-conferring single amino acid variants and the corresponding TKIs. Our comprehensive resistance map will complement clinical guidelines in drug selection for patients with chronic myeloid leukaemia based on ABL1 mutations, facilitating precision medicine.

Targeted immune therapies like blinatumomab, inotuzumab ozogamicin (InO), rituximab, and nelarabine are being combined with traditional chemotherapy protocols to enhance remission rates and minimal residual disease (MRD) negativity while decreasing toxicities...Ph + ALL patients receive standard treatment with multi-agent chemotherapy and TKIs dasatinib or ponatinib and blinatumomab as part of their frontline therapy to enhance molecular responses and minimize the requirement for allogeneic hematopoietic stem cell transplantation (allo-HCT)...The practice of testing MRD and genomic profiling at diagnosis revolutionized treatment approaches by allowing personalized curative strategies for all patients. Research on clinical trials aims to establish the best sequence of targeted therapies and CAR T-cell therapy for high-risk and MRD-positive patients to achieve longer survival rates with reduced toxicity and less dependence on allo-HCT in first remission.

We identified promising non-chemotherapeutic drug pairs, including trametinib-ponatinib and rapamycin-ganetespib and demonstrated potent synergistic effects. Surprisingly, alternating administration of nanoparticle drug pairs was superior to concomitant regimen in both efficacy, survival and toxicity profiles. These findings strengthen a functional approach for combinatorial personalized treatment, potentially overcoming the limitations of current therapeutic strategies.

Mechanistically, ponatinib directly inhibits p38α kinase activity, reducing signal transducer and activator of transcription 1 (STAT1) phosphorylation at Ser727 and suppressing CXCL1 and CXCL2 expression in cancer cells, thereby blocking MDSC infiltration. Our findings establish ponatinib as a novel inhibitor of MDSC-mediated immunosuppressive TME and underscore its therapeutic potential in combination with immune checkpoint blockade for TNBC treatment.

Ponatinib, regorafenib, and vandetanib are FDA-approved VEGFR, Tie2, and Ephrin receptor blockers used in the treatment of various malignancies. Other disorders characterized by aberrant angiogenesis include diabetic retinopathies and neovascular age-related macular degeneration.

P2, N=88, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027