Linperlisib plus CHOP for newly diagnosed peripheral T-cell lymphoma: A single-arm, phase Ib/II study (LINCH trial).

Abstract

7004 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous type of aggressive non-Hodgkin lymphoma with poor prognosis. CHOP-based regimens are most widely used for PTCL yet response rates and long-term survival remain unsatisfactory. Linperlisib, a selective PI3Kδ inhibitor, has shown encouraging antitumor activity with manageable safety profile in relapsed or refractory PTCL. This study aimed to evaluate the efficacy and safety of linperlisib plus CHOP (L-CHOP) as first-line treatment for newly diagnosed PTCL. Methods: The LINCH trial (NCT05949944), a multi-center, single-arm phase Ib/II study, enrolled patients aged ≥ 18 years with newly diagnosed PTCL. In phase Ib, 6 patients received 6 cycles of L-CHOP to determine the recommended phase II dose (RP2D). In phase II, patients received L-CHOP at the RP2D. Following 6 cycles, patients achieving complete response (CR) or partial response (PR) continued linperlisib maintenance until progression or intolerable toxicity or up to 24 months. The primary endpoints were the DLTs incidence (phase Ib) and the CR rate after 6 cycles of L-CHOP (phase II). Preliminary results were reported. Results: From August 15, 2023 to November 15, 2025, 44 patients were enrolled, including 6 patients in phase Ib. The median age was 57 years (range 18–77); 28 patients were males (63.6%). Most patients (n = 35, 79.5%) had stage III-IV disease, and 17 (38.6%) had an IPI score of 3–5. In phase Ib, one DLT (grade 3 febrile neutropenia) occurred in cycle 1, confirming linperlisib 80 mg once daily as RP2D. At the data cutoff on December 30, 2025, efficacy was evaluable in 34 patients (26 completed six cycles; 8 discontinued early), with 10 still receiving induction therapy. After six cycles of combination therapy, 19 patients (55.9%) achieved CR and four achieved PR, resulting in an objective response rate (ORR) of 67.6%. Treatment-emergent adverse events (TEAEs) occurred in 32 patients (94.1%); hematologic toxicity were common: neutropenia (n = 24, 70.6%), leukopenia (n = 21, 61.8%), anemia (n =14, 41.2%). Grade ≥ 3 TEAEs occurred in 19 patients (55.9%), most frequently neutropenia (n = 13, 38.2%), leukopenia (n = 10, 29.4%) and pneumonia (n = 4, 11.8%). Conclusions: Preliminary results from LINCH study suggest that linperlisib combined with CHOP as first-line treatment for PTCL achieved promising efficacy and manageable safety. A randomized controlled trial evaluating linperlisib plus CHOP versus CHOP in patients with newly diagnosed PTCL has been initiated (NCT06548347). Clinical trial information: NCT05949944 . Baseline characteristics. Characteristics Patients (n=44) Age, years (median [IQR]) 57 (18-77)  Sex  MaleFemale 28 (63.6%)16 (36.4%) ECOG PS  0-12 39 (88.6%)5 (11.4%) Lugano stage  I-II III-IV 9 (20.5%)35 (79.5%) Pathological types  AITLPTCL-NOSALCLTFHL-NOSMEITLSPTCL 23 (52.3%)14 (31.8%)3 (6.8%)2 (4.5%)1 (2.3%)1 (2.3%)