Background <p>This investigation assessed the therapeutic potential of combining linperlisib, a targeted inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), with gemcitabine and oxaliplatin (GEMOX) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).</p> Methods <p>This was a multicenter, phase Ib/II clinical study conducted across six sites in China, enrolling 39 individuals with histologically confirmed R/R DLBCL. The treatment protocol included oral linperlisib alongside GEMOX administered intravenously every three weeks for up to six cycles. The primary efficacy endpoint was the objective response rate (ORR).</p> Results <p>The ORR observed in the full study population was 53.8% (95% confidence interval [CI]: 37.2–69.9). The median duration of response was 5.7 months (95% CI: 4.3–9.1), and the median progression-free survival was 5.4 months (95% CI: 1.8–6.7). The 1-year OS rate was 65.5% (95% CI: 48.1–78.3). Frequently observed adverse events included decreases in neutrophil counts (74.4%), white blood cell counts (64.1%) and platelet counts (64.1%).</p> Conclusions <p>This study highlights the potential of linperlisib plus GEMOX as a treatment for R/R DLBCL, demonstrating a tolerable safety profile and encouraging efficacy results.</p> Trial registration <p>NCT04500561.</p>