Our results demonstrated that the combination of T-DXd, anti-SIRPα, and IPI-549 significantly inhibited tumor growth compared to monotherapies, with no major weight loss, indicating a favorable tolerability profile. Importantly, previously treated mice developed durable immunological memory, completely rejecting subsequent challenges with HER2-expressing tumors. Overall, these findings highlight the therapeutic potential of combining T-DXd with macrophage-targeting strategies as a robust approach to improve the efficacy of immunotherapy in HER2-positive cancers, presenting a promising avenue for clinical development.

P1, N=14, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Apr 2024

P2, N=40, Recruiting, Rhizen Pharmaceuticals SA | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P2, N=26, Active, not recruiting, Glenn J. Hanna | Trial completion date: Jan 2025 --> Jan 2026

P2, N=156, Completed, SecuraBio | N=103 --> 156

P2, N=170, Recruiting, Alliance for Clinical Trials in Oncology | Trial completion date: Jan 2026 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P1, N=70, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting | N=49 --> 70 | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

P1/2, N=12, Not yet recruiting, Jonsson Comprehensive Cancer Center

P1, N=14, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2025 --> Jun 2025

P1, N=72, Recruiting, Kither Biotech Srl | Active, not recruiting --> Recruiting

P1, N=4, Completed, Emory University | Recruiting --> Completed | N=20 --> 4 | Trial completion date: Aug 2025 --> Sep 2024 | Trial primary completion date: Aug 2024 --> Mar 2024

CFI-402257, a specific inhibitor of TTK, is found to exhibit anti-tumor effects and exerted synergistic efficacy with PI3K inhibitor, Duvelisib, in TCL. The study shows that TTK contributes to the development of TCL by regulating p38α-mediated AMPK/mTOR pathway. CFI-402257 is expected to be a promising strategy for TCL treatment.

P2, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025

P1, N=72, Active, not recruiting, Kither Biotech Srl | Recruiting --> Active, not recruiting

These include single-agent brentuximab vedotin, histone deacetylase inhibitors, duvelisib, ruxolitinib, EZH2 inhibitors, and azacitidine, among others. Follicular helper T-cell lymphomas, given frequent mutations in epigenetic regulator genes, may preferentially respond to agents such as histone deacetylase inhibitors, EZH2 inhibitors, and hypomethylating agents. As these therapies evolve in their use for both relapsed/refractory disease and then into frontline treatment, subtype-specific therapy will likely help personalize care for patients with PTCL.

We report a favorable response rate when combining a selective PI3K pathway inhibitor and taxane in patients with anti-PD-1 refractory HNSCC.

P3, N=124, Not yet recruiting, SecuraBio | Initiation date: Dec 2024 --> Mar 2025

P1/2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Phase classification: P1b/2 --> P1/2

P1/2, N=40, Completed, Nanjing Zenshine Pharmaceuticals | Recruiting --> Completed | N=70 --> 40

P1, N=72, Recruiting, Kither Biotech Srl

The therapeutic effect of various nanohybrids were validated in the mice with spontaneous tumor in the colorectal area and tumor-bearing mice, which lead to the increase of ferroptosis, the activation of STING signaling pathway, and the repolarization of macrophages. Collectively, the cGAMP and IPI-549 co-loaded nanohybrids effectively reshaped the tumor immune microenvironment, and exhibited prominent treatment effect of anti-colorectal cancer in vitro, patient-derived organoids, and in vivo.

This is the first report of translational analyses including paired tumor biopsies from a phase 2 clinical study of the first-in-class PI3K-γ inhibitor eganelisib in combination with atezolizumab and nab-paclitaxel in frontline mTNBC. These results support the mechanism of action of eganelisib as a TAM-reprogramming immunotherapy and support the rationale for combining eganelisib with ICI and chemotherapy in indications with TAM-driven resistance to ICI.

Herein we describe the identification of a novel gene fusion SMCHD1::JAK2 resulting from a translocation between chromosome 9 and 18 involving SMCHD1 exon 45 and JAK2 exon 14 (t(9;18)(p24.1;p11.32)(chr9:g.5080171::chr18:g.2793269)), a previously undescribed genetic event in a patient with T-PLL harboring the key disease defining inv(14) resulting in rearrangement of TCL1 and TRA/D. In this manuscript, we describe the clinical and genetic features of the patient's disease course over a 25-month post-treatment duration using ruxolitinib and duvelisib.

P1/2, N=13, Active, not recruiting, John Kirkwood | Recruiting --> Active, not recruiting | N=42 --> 13 | Trial completion date: Oct 2029 --> Dec 2028 | Trial primary completion date: Apr 2028 --> Feb 2024

P2, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2024 --> Dec 2024

The predominant PI3Kγ inhibitors were IPI-549 and TG100-115, demonstrating favourable specificity for the gamma isoform. The combination of PI3Kγ inhibition with other therapeutic modalities demonstrated enhanced antitumour effects, suggesting a synergistic approach to overcome immune suppression. These findings support the potential of PI3Kγ-targeted therapies, particularly in combination regimens, as a promising avenue for future clinical exploration in diverse solid tumour types.

P1, N=125, Not yet recruiting, Stelexis BioSciences

P1/2, N=67, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Dec 2024

P3, N=124, Not yet recruiting, SecuraBio

P2, N=17, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | N=36 --> 17 | Trial completion date: Jul 2027 --> Jul 2026 | Trial primary completion date: Jul 2027 --> Jul 2026

P1, N=114, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

P1/2, N=42, Recruiting, John Kirkwood | Trial completion date: Oct 2028 --> Oct 2029 | Trial primary completion date: Apr 2027 --> Apr 2028

In addition, the combination of eganelisib and cytarabine prolongs survival over either agent alone, even in patient-derived leukaemia xenografts with low baseline PIK3R5 expression, as residual leukaemia cells after cytarabine treatment have elevated G protein-coupled purinergic receptor activity and PAK1 phosphorylation. Together, our study reveals a targetable dependency on PI3Kγ-PAK1 signalling that is amenable to near-term evaluation in patients with acute leukaemia.

Two PIK3CG-specific inhibitors, Eganelisib and CAY10505, were used to treat A549 and H1299 cells...Co-culture with neutrophils, soluble extracts of neutrophils and cathepsin G all promoted the migration of lung cancer cells. PIK3CG overexpression in tumor cells significantly promoted the migration and metastasis of lung cancer cell.

P1, N=49, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P1, N=14, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=30 --> 14 | Trial completion date: Oct 2025 --> Mar 2025 | Trial primary completion date: Oct 2025 --> Mar 2024

Finally, analyses implied Duvelisib and Eganelisib as promising dual-purposed anti-COVID and anticancer drugs, potentially targeting Mpro and PI3Kγ to stop virus replication and cytokine storms concomitantly. We also distinguished hotspot residues imparting significant interactions.

Moreover, our investigation has shown that AZD2014, SB505124, LJI308 and OSI-207 show a greater efficacy in patients in the low-risk category. Conversely, for the high-risk group patients, PD173074, ZM447439 and CZC24832 exhibit a stronger response...This innovative model provides a novel approach for forecasting prognosis and assessing drug sensitivity in HCC patients, driving a more personalized and efficacious treatment paradigm, elevating clinical outcomes. Nonetheless, additional research endeavours are required to confirm the model's precision and assess its potential to inform clinical decision-making for HCC patients.

P1, N=43, Recruiting, Washington University School of Medicine | Trial completion date: Oct 2029 --> May 2030 | Trial primary completion date: May 2025 --> Dec 2025

P2, N=40, Recruiting, Rhizen Pharmaceuticals SA | Not yet recruiting --> Recruiting

P1, N=30, Active, not recruiting, Boryung Pharmaceutical Co., Ltd | Recruiting --> Active, not recruiting

P2, N=15, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024