HanchorBio Inc., a global biotechnology company developing innovative immuno-biomedicines to address significant unmet medical needs in oncology, today announced that the Taiwan Food and Drug Administration (TFDA) has approved a second investigator-initiated trial (IIT) evaluating the safety and efficacy of HCB101 in combination with pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who are refractory to platinum-based chemotherapy. The study will take place at Taipei Veterans General Hospital and Linkou Chang Gung Memorial Hospital. This marks the second TFDA-approval IIT of HCB101 in combination with standard-of-care (SOC) therapies, following the recently announced IIT approval for a metastatic colorectal cancer (mCRC) study. The new approval underscores HanchorBio’s strategic focus on expanding HCB101’s clinical development MOA (mode of action) based immunotherapy combinations across multiple solid tumors with unmet medical needs.
“Head and neck squamous cell carcinoma remains a formidable challenge, particularly in patients who have progressed following standard therapies,” said Scott Liu, Ph.D., Founder, Chairman, and Chief Executive Officer of HanchorBio. “Increasing amounts of evidence point to CD47 as a key driver of immune escape in more than 15 different tumors. By combining an anti-PD-1 therapy with HCB101, a specially designed and engineered SIRPα-Fc fusion having dramatically increased capability to block the CD47 “don’t eat me” signal, we aim to reinvigorate exhausted T cells while enhancing macrophage activation and tumor antigen presentation. The enhanced tumor antigen presentation will, in turn, activate T cells, leading to more durable clinical responses. This second TFDA-approved IIT reflects our endeavor to position HCB101 as a wide-spectrum, foundational immunotherapy backbone for multiple solid tumors and reinforces our commitment to advancing rational, mechanism-based combination therapies that can potentially improve the clinical outcomes for millions of cancer patients.”
About the Investigator-Initiated Trial in Advanced or Metastatic Head and Neck Cancer
The non-randomized, open-label, dose-escalation, and dose-expansion trial (HCB101-IIT-HNSCC-202401) is designed to evaluate the safety, tolerability, and efficacy of HCB101 in combination with pembrolizumab in patients with cisplatin refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) who have progressed following prior systemic therapy.
- Trial Sponsor: Taipei Veterans General Hospital and Linkou Chang Gung Memorial Hospital
- Principal Investigators: Dr. Peter Mu-Hsin Chang and Dr. Chia-Hsun Hsieh
HCB101 Combination Rationale
HCB101 is an engineered SIRPα fusion protein developed through AI-assisted structural modeling and large-scale screening of a phage library containing 100 million different SIRPα variants. It is specifically designed to selectively and effectively block the CD47-SIRPα “don’t eat me” signal to enhance antibody-dependent cellular phagocytosis (ADCP) and bridge innate and adaptive immune responses while maintaining a favorable safety profile. Preclinical data suggest that CD47 blockade can synergize with immune checkpoint inhibitors to reshape the tumor microenvironment (TME) and overcome resistance to current immunotherapies.
- HCB101 + Pembrolizumab:
Recurrent/metastatic HNSCC is characterized by a highly immunosuppressive TME and low response rates to PD-1 inhibitors (~20%), marked by dysfunctional antigen presentation, T-cell exhaustion, infiltration of immune-suppressive myeloid populations, and resistance to checkpoint blockade. HCB101 aims to enhance pembrolizumab’s anti-tumor activity by increasing macrophage activation, promoting dendritic cell maturation, and boosting tumor-specific T-cell infiltration while also shifting the macrophage phenotype from immunosuppressive M2 to pro-inflammatory M1. Preclinical studies using syngeneic HNSCC models (e.g., MOC1, ROC1) have demonstrated that anti-CD47 and anti-PD-1/PD-L1 therapies produce greater tumor regression and survival benefit than either agent alone (Wu et al., Oncoimmunology 2018).
Given pembrolizumab’s established role in HNSCC and the emerging evidence that PD-1 blockade induces compensatory upregulation of CD47, the combination of HCB101 and pembrolizumab is strategically designed to address both innate and adaptive resistance mechanisms. By co-targeting the CD47-SIRPα and PD-1 pathways, this dual approach may reinvigorate exhausted T cells, increase the depth of response, and convert non-inflamed (“cold”) tumors into immunologically active (“hot”) tumors in patients with limited treatment options.
“This IIT provides a promising opportunity to explore the synergy of CD47 blockade with PD-1 inhibition in immunologically ‘cold’ tumors like HNSCC,” said Dr. Peter Mu-Hsin Chang, Principal Investigator. “By targeting both innate and adaptive resistance mechanisms, we hope this combination strategy will generate more durable anti-tumor responses for patients with limited treatment options.”
About HCB101: A Differentiated CD47-SIPRα Blockade
HCB101 is a potential best-in-class Fc-fusion SIRPα variant designed to optimize immune activation while minimizing hematologic toxicity. Unlike traditional anti-CD47 monoclonal antibodies, HCB101 demonstrates selective tumor engagement with low red blood cell (RBC) binding, reducing the risk of anemia and thrombocytopenia commonly observed with other CD47-targeting agents.
Key Differentiators of HCB101:
- Enhanced safety profile: Reduced RBC depletion compared to traditional CD47-targeting agents.
- Synergistic immune activation: Strongly enhanced ADCP, bridging innate and adaptive immune responses to drive durable anti-tumor immunity.
- Broad anti-tumor spectrum: Demonstrated tumor growth inhibition activities in over 78 CDX and PDX preclinical models across multiple solid tumors and hematological malignancies.
HCB101 is currently being evaluated in multiple clinical trials, including:
- HCB101-101 (NCT05892718): A Phase 1 open-label, multi-regional, multi-center, dose-finding, first-in-human monotherapy trial of HCB101 in advanced solid tumors or relapsed and refractory non-Hodgkin lymphomas.
- HCB101-201 (NCT06771622): A Phase 1b/2a open-label, multi-regional, multi-center trial of HCB101 in combination with standard-of-care therapies in advanced solid tumors.
- HCB101-IIT-CRC-202401: An open-label, dose-escalation, and dose-expansion investigator-initiated trial of HCB101 in combination with cetuximab or bevacizumab and chemotherapy regimens in RAS/BRAF wild-type advanced or metastatic colorectal cancer.
- HCB101-IIT-HNSCC-202401: A non-randomized, open-label, dose-escalation, and dose-expansion investigator-initiated trial of HCB101 in combination with pembrolizumab in patients with cisplatin-refractory, recurrent or metastatic head and neck squamous cell carcinoma (SirH&N Trial).
About HanchorBio
Based in Taipei, Shanghai, and the San Francisco Bay Area, HanchorBio, a global biotechnology company focusing on immuno-oncology, is led by an experienced team of pharmaceutical industry veterans with a proven track record of success in biologics discovery and global development to rewrite cancer therapies. Committed to reactivating the immune system to fight against diseases, the proprietary Fc-based designer biologics (FBDB™) platform enables unique biologics with diverse multi-targeting modalities to unleash both innate and adaptive immunity to overcome the current challenges of anti-PD1/L1 therapies. The FBDB™ platform has successfully delivered proof-of-concept data in several in vivo tumor animal models. By making breakthroughs in multi-functional innovative molecular configurations in R&D and improving the manufacturing process in CMC, HanchorBio develops transformative medicines to address unmet medical needs.