Abstract
BACKGROUND: Immune checkpoint inhibitors achieve high response rates in relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL), but few treatment options are available for patients who experience failure after PD-1/PD-L1 blockade. T cell immunoglobulin and mucin-domain containing-3, a key mediator of immune escape from PD-1/PD-L1 inhibition, is targeted by TQB2618, a humanized IgG(4) monoclonal antibody. This phase Ib study aimed to evaluate the safety and efficacy of TQB2618 in combination with the anti-PD-1 antibody penpulimab in patients with r/r cHL. METHODS: This multicenter phase 1b study was conducted from June 2022 to September 2024 at 12 sites in China (NCT05400876). The study included a dose-escalation phase in which patients with r/r lymphoma received TQB2618 (600 or 1200 mg, every 3 weeks, Q3W) plus penpulimab (200 mg, Q3W) to evaluate dose-limiting toxicities and determine the recommended phase II dose (RP2D). The subsequent dose-expansion phase enrolled patients with r/r cHL previously treated with PD-1/PD-L1 inhibitors to assess the objective response rate (ORR). RESULTS: 10 patients with r/r lymphoma were enrolled in the dose-escalation phase, and TQB2618 (600 mg, Q3W) plus penpulimab (200 mg, Q3W) was selected as the RP2D. In the dose-expansion phase, 18 additional patients with r/r cHL previously treated with PD-1/PD-L1 inhibitors were enrolled. Among the total 21 r/r cHL patients, the median age was 32 years (range, 22-65), and 12 (57%) were male. The ORR was 52%, including 1 complete response and 10 partial responses. Treatment-related adverse events (TRAEs) occurred in 18 patients (86%), with grade ≥3 TRAEs in 5 (24%). The most common TRAEs (≥20%) were platelet count decreased (24%), anemia (24%), and aspartate aminotransferase increased (24%). As of the data cut-off in December 2024, the median follow-up was 14.1 months, the median duration of response and the median overall survival had not yet been reached. CONCLUSIONS: TQB2618 in combination with penpulimab was well tolerated and demonstrated promising efficacy in patients with cHL who had failed prior anti-PD-1/PD-L1 therapy, supporting its potential as a therapeutic option for this difficult-to-treat population. TRIAL REGISTRATION NUMBER: NCT05400876.