P2, N=170, Suspended, Alliance for Clinical Trials in Oncology | Trial completion date: Jun 2026 --> May 2027 | Trial primary completion date: Jun 2026 --> May 2027

Interestingly, leniolisib, a selective PI3Kδ kinase inhibitor, has been approved for the rare disease Activated Phosphoinositide 3-kinase Delta Syndrome (APDS)...We hereby explored the implication of PI3K signaling in diabetic retinopathy. Moreover, we reviewed the current literature to highlight molecular features of class I PI3K selective inhibitors, to further guide the design of novel selective and safe drugs targeting PI3Kδ, for management of diabetic retinopathy or other retinal proliferative diseases.

P1, N=210, Active, not recruiting, iOnctura | Trial completion date: Mar 2025 --> Mar 2027

Full tumour control, however, was achieved when IOA-244 used in a combinatorial regimen with the PF-8380 ATX inhibitor. In agreement with the mouse model, the amount of CD163+/CD204+macrophages and ATX were much higher in grade III human breast carcinomas compared to grade I. Our work provides the first in vivo preclinical evidence showing that IOA-244 is a potential highly effective drug for breast cancer treatment and depending on the phase of the tumour can be used either as a single agent or as a combinatorial regimen.

Overall, duvelisib plus venetoclax was active in high-risk R/R CLL/SLL and RT, though serious adverse events occurred, including immune-mediated toxicities. NCT03534323.

Here, we show that combining the PI3Kδ inhibitor linperlisib with the pan-peroxisome proliferator-activated receptor (PPAR) agonist chiglitazar, an agent that reprograms tumor metabolism, delivers robust antitumor activity across FL models, including cell-derived and patient-derived xenografts, with a favorable tolerability profile. Compared with monotherapy, the combination consistently achieves superior tumor control in vivo without overt toxicity, supporting its clinical translation potential. Collectively, these data provide a mechanistic rationale for dual targeting of PI3Kδ and PPARα in FL and advocate for clinical evaluation of this combination with FoxO1 as a pharmacodynamic biomarker.

P2, N=150, Active, not recruiting, Calluna Pharma AS | Recruiting --> Active, not recruiting

This approach enabled the rational design of copanlisib-based PROTACs, with top compound D5 achieving catalytic degradation efficiency (PI3Kα DC50 = 0.05 nM in T47D cells), >10,000-fold degradation selectivity over the PI3Kβ and PI3Kγ isoforms and minimal off-target effects across >7000 profiled proteins...Orally administered D5 (40 mg/kg) significantly inhibited tumor growth (65% TGI) in xenograft models without inducing metabolic dysregulation. D5 may offer a therapeutic option for human breast cancer harboring the PIK3CA H1047R mutation.

P1/2, N=6, Active, not recruiting, Pharming Technologies B.V. | Recruiting --> Active, not recruiting

Fifty-three patients received treatment after venetoclax: 29/53 (54.7%) received inhibitors (13 cBTKi, 11 idelalisib, 2 BCL2i, 3 non-covalent BTKi), 19/53 (35.8%) received chemoimmunotherapy (CT: 16 intensive, 3 palliative), 5/53 (9.4%) received hematopoietic stem cell transplantation (HSCT). Despite its limitations, this real-world study provides additional insights into double-exposed patients, who still pose a clinical challenge, demonstrating the superior efficacy of inhibitors over alternative treatment options. Enrollment in clinical trial and treatments with novel molecules, if available, may help address this unmet clinical need.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

P2, N=22, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027