{
  "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.",
  "authors": [
    {
      "affiliations": [
        "Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, China"
      ],
      "name": "Huangming Hong"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "Zegeng Chen"
    },
    {
      "affiliations": [
        "Department of Hematology, Gansu Provincial Cancer Hospital, Lanzhou, Gansu, China"
      ],
      "name": "Jie Cui"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China"
      ],
      "name": "Qingyuan Zhang"
    },
    {
      "affiliations": [
        "Department of Hematology, Shanghai Tongji Hospital, Shanghai, China"
      ],
      "name": "Ping Li"
    },
    {
      "affiliations": [
        "Fudan University Shanghai Cancer Center, Shanghai, China"
      ],
      "name": "Rong Tao"
    },
    {
      "affiliations": [
        "State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China"
      ],
      "name": "He Huang"
    },
    {
      "affiliations": [
        "Weihai Municipal Hospital, Weihai, Shandong, China"
      ],
      "name": "Binghua Wang"
    },
    {
      "affiliations": [
        "Jiangxi Cancer Hospital, Nanchang, Jiangxi, China"
      ],
      "name": "Wuping Li"
    },
    {
      "affiliations": [
        "Fujian Cancer Hospital, Fuzhou, Fujian, China"
      ],
      "name": "Hui Wu"
    },
    {
      "affiliations": [
        "Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China"
      ],
      "name": "Jin Wei"
    },
    {
      "affiliations": [
        "Shanxi Cancer Hospital, Taiyuan, Shanxi, China"
      ],
      "name": "Liping Su"
    },
    {
      "affiliations": [
        "Chengde Medical University Affiliated Hospital, Chengde, Hebei, China"
      ],
      "name": "Zhihua Zhang"
    },
    {
      "affiliations": [
        "Ganzhou People’s Hospital, Ganzhou, Jiangxi, China"
      ],
      "name": "Mingxing Zhong"
    },
    {
      "affiliations": [
        "Tianjin City People’s Hospital, Tianjin, China"
      ],
      "name": "Huaqing Wang"
    },
    {
      "affiliations": [
        "Wuwei Cancer Hospital of Gansu Province, Lanzhou, Gansu, China"
      ],
      "name": "Cong Wang"
    },
    {
      "affiliations": [
        "Hunan Cancer Hospital, Changsha, Hunan, China"
      ],
      "name": "Hui Zhou"
    },
    {
      "affiliations": [
        "The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China"
      ],
      "name": "Jishi Wang"
    },
    {
      "affiliations": [
        "The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China"
      ],
      "name": "Min Dong"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, China"
      ],
      "name": "Tongyu Lin"
    }
  ],
  "title": "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",
  "uid": "25f30a7d-fd2e-5f24-b61b-75976e72388f"
}