Anti-TIM-3 antibody TQB2618 in combination with penpulimab in relapsed or refractory classic Hodgkin lymphoma previously treated with PD-1/PD-L1 therapy: a multicenter, open-label, single-arm, phase Ib clinical trial

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: 52% ORR including 1 complete response and 10 partial responses

• Primary Outcome: Objective response rate of 52% (11/21 patients)

• Nnt Or Sensitivity: Number needed to treat approximately 2 for one response

• Confidence Interval: Not reported

Clinical Application

Requires specialized oncology centers with experience in immunotherapy combinations; IV administration every 3 weeks Would require TGA approval; not currently PBS-listed; limited treatment options exist for this population in Australia, making this potentially valuable Patients with relapsed/refractory classical Hodgkin lymphoma who have failed prior PD-1/PD-L1 therapy

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 IgG4 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.

References

1. 1.Hong, H., Chen, Z., Cui, J., Zhang, Q., Li, P., Tao, R., Huang, H., Wang, B., Li, W., Wu, H., Wei, J., Su, L., Zhang, Z., Zhong, M., Wang, H., Wang, C., Zhou, H., Wang, J., Dong, M., & Lin, T. (2026). Anti-TIM-3 antibody TQB2618 in combination with penpulimab in relapsed or refractory classic Hodgkin lymphoma previously treated with PD-1/PD-L1 therapy: a multicenter, open-label, single-arm, phase Ib clinical trial. Journal for Immunotherapy of Cancer. https://doi.org/10.1136/jitc-2026-014968