P1, N=20, Not yet recruiting, Roswell Park Cancer Institute

An ICB-resistant B16F10 melanoma tumor model was established, and we further verified that the combined treatment with MerTK inhibitor UNC2025 and anti-mouse PD-1 recombinant mAb effectively restored the ICB treatment efficacy...Our findings indicate that [68Ga]Ga-MerTKi PET can potentially identify patients who may benefit from ICB therapy alone and who may need combination therapy. This observation supports the use of MerTK PET as a tool to guide more personalized treatment in cancer immunotherapy.

In vivo, WDR12 targeting sensitizes tumors to PD-1 blockade, and combined SU14813 and anti-PD-1 therapy produces superior antitumor efficacy. These results define a WDR12-CCT7-CD276 axis that sustains immune resistance in melanoma and nominate WDR12 inhibition with PD-1 blockade as a promising therapeutic strategy.

In conclusion, the addition of Quizartinib to intensive chemotherapy, delayed until chemotherapy course 2, prolonged OS in older patients with FLT3-mutated AML but did not improve OS in non-FLT3 selected patients. ISRCTN-31682779, EudraCR-2013-002730-21.

P1/2, N=70, Recruiting, Ellipses Pharma | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2027

In recent years, oral therapy with the JAK1/2 inhibitor ruxolitinib has become the standard of care. Since 2021, the JAK2/FLT3 inhibitor fedratinib has also been approved in the EU (note: in Switzerland, fedratinib will no longer be available as of February 28, 2025, as Swissmedic did not extend its time-limited approval)...Compared to the other two JAK inhibitors, momelotinib is particularly effective in patients with clinically symptomatic moderate to severe anemia. Results from studies investigating additional JAK inhibitors, combination therapies, and novel agents have also demonstrated significant efficacy and point toward future therapeutic developments, although these approaches are not yet available for routine clinical practice.

Second-generation FLT3 inhibitors significantly improve survival outcomes in FLT3-mutated AML, particularly for gilteritinib and in relapsed/refractory disease. Further studies are needed to clarify mutation subtype-specific and dose-specific effects.

The risk-based approach and use of targeted therapies in CHIP-AML22 illustrate a shift toward more personalized treatment. Besides improving event-free survival, this study aims to contribute to the international consensus on strategies to reduce toxicity for all patients. The design of this study provides a dynamic framework, allowing for the potential introduction of emerging therapeutic options in the future.

Notably, the combination of 6k and the FLT3 inhibitor quizartinib showed significant synergistic antiproliferative effects both in vitro and in vivo. Mechanistic studies showed that this combined strategy could simultaneously inhibit glycolysis and OXPHOS by blocking the PI3K/AKT signaling pathway, ultimately exerting antitumor activity. In summary, this study highlights 6k as a potential metabolic regulator and provides a promising therapeutic strategy for AML.

P2, N=25, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

These results suggest that concomitant use of quizartinib and moderate CYP3A inducers should be avoided. Concomitant use of weak CYP3A inducers does not warrant dose adjustment, since the impact on quizartinib exposure is clinically nonrelevant.

P2/3, N=207, Active, not recruiting, Sobi Inc. | Recruiting --> Active, not recruiting