{
  "abstract": "Background CD47-SIRPα blockade is a validated immuno-oncology strategy, earlier agents were limited by hematologic toxicities and limited clinical benefit, resulting in program discontinuation and clinical hold. HCB101 is a novel, Fc-engineered human SIRPα-IgG4 fusion protein developed using the proprietary FBDB™ platform. It is designed to selectively block SIRPα-CD47 interactions, restore macrophage-mediated phagocytosis, and promote adaptive antitumor immunity while minimizing red blood cell binding. Preclinical studies demonstrated potent antitumor activity across solid and hematological malignancies without on-target hematologic toxicity, supporting its first-in-human evaluation.Methods This ongoing multinational, open-label, Phase 1 dose-escalation study enrolled adults with relapsed/refractory solid tumors or non-Hodgkin lymphoma (NHL). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Using a Bayesian Optimal Interval (BOIN)-adapted 3+3 design, HCB101 was administered intravenously once weekly (0.08-30.0 mg/kg). Primary endpoints were safety and tolerability; secondary endpoints included objective response rate, duration of response, and progression-free survival (PFS). Exploratory endpoints included pharmacokinetics (PK), CD47 receptor occupancy (RO), peripheral immune profiling, and biomarker analyses.Results As of August 27, 2025, 55 participants (71% solid tumors, 29% NHL) received HCB101. Treatment-related adverse events (TRAEs) were manageable, most commonly cytopenias (white blood cell 20.8%, platelet 13.2%, and lymphocyte 11.3%), anemia (18.9%), and infusion-related reactions (13.2%). Among 48 DLT-evaluable participants, one DLT (Grade 3 thrombocytopenia received platelet transfusion) at 2.56 mg/kg resolved within 6 days. No maximum tolerated dose was reached through 24.0 mg/kg, establishing a broad therapeutic window with dose-proportional PK. Peripheral CD47 RO was ≥90% at ≥1.28 mg/kg and ≥99% at ≥5 mg/kg, consistent with durable target engagement.Clinical efficacy included 9 participants with stable disease, 2 with PFS ≥22 weeks, and 1 with PFS of 40 weeks. Two confirmed partial responses (PRs) were observed: one head and neck squamous cell carcinoma (HNSCC) at 5.12 mg/kg (27% reduction at Week 8, deepening to 42% by Week 24), and one marginal zone lymphoma at 8.00 mg/kg.Conclusions HCB101 demonstrates favorable safety, consistent high receptor occupancy, and early durable activity across advanced solid and hematologic malignancies. Compared with earlier CD47-targeting agents, HCB101 showed a differentiated safety and pharmacologic profile, with encouraging disease control and partial responses in monotherapy. These data support tumor-specific cohort expansions and rational combination strategies currently underway, positioning HCB101 as a promising next-generation CD-47 innate immune checkpoint therapy.Trial Registration This trial is registered on clinicaltrials.gov NCT05892718Ethics Approval The study was approved by following ethics committees: 1.WCG Institutional Review Board (the United States); Number of the approval: 20232351; 2. TAIPEI VETERANS GENERAL HOSPITAL Institutional Review Board (Taiwan); Number of the approval: 2023-09-001BU#5; 3.Research Ethics Committee C National Taiwan University Hospital (Taiwan); Number of the approval: 202307200MSC; 4. TMU Joint Institutional Review Board (Taiwan); Number of the approval: N202306051; 5. Fudan University Shanghai Cancer Center Ethics Committee; Number of the approval: 2408301-16; 6. Hangzhou First People’s Hospital Ethics Committee; Number of the approval: 2024-179-05; 7. Guangdong Provincial People’s Hospital Ethics Committee; Number of the approval: YW2024-108-07; 8. Cancer Hospital of Shandong First Medical University Ethics Committee; Number of the approval: SDZLEC2024-310-04; 9. Binzhou Medical University Affiliated Hospital Ethics Committee; Number of the approval: 2025-031-02; 10. Dezhou Hospital of Qilu Hospital of Shandong University Ethics Committee; Number of the approval: 2025-008-003.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.",
  "authors": [
    {
      "affiliations": [
        "HanchorBio Inc, Kowloon, Hong Kong"
      ],
      "name": "Langtian Abigail Yu"
    },
    {
      "affiliations": [
        "Binzhou Medical University Affiliated Hospital, Binzhou, Shandong, China"
      ],
      "name": "Fangling Ning"
    },
    {
      "affiliations": [
        "Binzhou Medical University Affiliated Hospital, Binzhou, Shandong, China"
      ],
      "name": "Lijun Tian"
    },
    {
      "affiliations": [
        "Cancer Hospital of Shandong First Medical University, Jinan, Shandong, China"
      ],
      "name": "Ji Ma"
    },
    {
      "affiliations": [
        "Hematology Oncology Associates of the Treasure Coast, St. Port Lucie, FL, USA"
      ],
      "name": "Nicholas O Iannotti"
    },
    {
      "affiliations": [
        "National Taiwan University Hospital, Taipei, Taiwan"
      ],
      "name": "Chia-Chi Lin"
    },
    {
      "affiliations": [
        "Shuang Ho Hospital, Zhonghe District, Taipei, Taiwan"
      ],
      "name": "Wei-Hong Cheng"
    },
    {
      "affiliations": [
        "Hangzhou First People’s Hospital, Hangzhou, Zhejiang, China"
      ],
      "name": "Ying Wang"
    },
    {
      "affiliations": [
        "Taipei Veterans General Hospital, Taipei, Taipei, Taiwan"
      ],
      "name": "Peter Mu-Hsin Chang"
    },
    {
      "affiliations": [
        "Prisma Health, Greenville, SC, USA"
      ],
      "name": "William J Edenfield"
    },
    {
      "affiliations": [
        "Guangdong Provincial People’s Hospital, ZHUHAI, Guangzhou, China"
      ],
      "name": "Wenyu Li"
    },
    {
      "affiliations": [
        "University of Texas Southwestern Medical Center, Dallas, TX, USA"
      ],
      "name": "Tian Zhang"
    },
    {
      "affiliations": [
        "Fudan University Shanghai Cancer Center, Shanghai, China"
      ],
      "name": "Jian Zhang"
    },
    {
      "affiliations": [
        "Dezhou Hospital of Qilu Hospital of Shandong University, Dezhou, Shandong, China"
      ],
      "name": "Guohua Chen"
    },
    {
      "affiliations": [
        "HanchorBio Inc, George Town, Grand Cayman, Cayman Islands"
      ],
      "name": "JunJie Li"
    },
    {
      "affiliations": [
        "HanchorBio Inc, George Town, Grand Cayman, Cayman Islands"
      ],
      "name": "Charles Wang"
    },
    {
      "affiliations": [
        "HanchorBio Inc, George Town, Grand Cayman, Cayman Islands"
      ],
      "name": "Zhili Zhou"
    },
    {
      "affiliations": [
        "HanchorBio Inc, George Town, Grand Cayman, Cayman Islands"
      ],
      "name": "Chih-Yi Hsieh"
    },
    {
      "affiliations": [
        "HanchorBio Inc, George Town, Grand Cayman, Cayman Islands"
      ],
      "name": "Alvin Luk"
    },
    {
      "affiliations": [
        "HanchorBio Inc, George Town, Grand Cayman, Cayman Islands"
      ],
      "name": "Vivien Zhang"
    },
    {
      "affiliations": [
        "HanchorBio Inc, George Town, Grand Cayman, Cayman Islands"
      ],
      "name": "David W Sun"
    }
  ],
  "title": "1331 HCB101, a next-generation Fc-engineered anti-CD47 SIRPα fusion protein, demonstrates favorable safety and early antitumor activity in advanced cancers",
  "uid": "0eae3d24-3720-5f0d-a36a-6869a48aad14"
}