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.
漢康生技(HanchorBio Inc.)，一家致力於開發創新免疫生物療法，以實現腫瘤學領域重大未被滿足醫療需求的全球生物技術公司，今日宣布台灣食品藥物管理署(TFDA)已核准第二項由研究者發起的臨床試驗（IIT），評估HCB101聯合pembrolizumab（帕博利珠單抗）治療接受過鉑類化療後復發或轉移的頭頸部鱗狀細胞癌（HNSCC）患者的安全性及療效。該研究將於台北榮民總醫院與林口長庚紀念醫院進行。本次核准是繼先前公告的轉移性結直腸癌（mCRC）IIT之後，第二項HCB101聯合標準治療（SOC）獲得TFDA核准的臨床試驗，顯示漢康生技的策略重點在於，透過拓展HCB101以生物機轉為基礎的免疫療法組合，開發多種實體瘤中的臨床應用。
「頭頸部鱗狀細胞癌在歷經標準療法後的病人中，仍是一種難治性腫瘤，」漢康生技創始人、董事長兼執行長劉世高博士表示，「越來越多證據指出，CD47是超過15種腫瘤中，免疫逃脫及PD-1阻斷療法抗藥性的關鍵因素之一。我們透過將抗 PD-1 療法與 HCB101 結合使用，HCB101是一種精心設計與工程優化的 SIRPα-Fc 融合蛋白，能大幅提升阻斷 CD47“別吃我”訊號的能力，進而重新活化 T 細胞，同時增強巨噬細胞的活性與腫瘤抗原的呈現。而增強的腫瘤抗原呈現又將進一步活化 T 細胞，帶來更長效的作用。此次第二度獲得 TFDA 批准的研究者自行發起(IIT)臨床試驗，說明我們在 HCB101 定位上，達成建立多種實體腫瘤的廣譜性及基礎免疫療法台，證實了我們的承諾──推動合理聯合治療機制的療法，期望為數百萬癌症患者帶來更佳的臨床結果。
HCB101是一種高選擇性的CD47-SIRPα通路抑制劑，透過與抗PD-1疊加使用，我們希望重塑免疫抑制的腫瘤微環境，恢復T細胞功能，並促進更持久的臨床療效。這項第二個由TFDA核准的研究者發起試驗，進一步展現我們將HCB101作為免疫治療基礎藥物發展藍圖的策略。我們將持續推進具科學依據的聯合療法組合，造福更多癌症患者。」
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關於晚期頭頸癌的研究者發起臨床試驗
這項非隨機、開放標籤、劑量遞增及劑量擴展試驗(HCB101-IIT-HNSCC-202401)旨在評估HCB101聯合帕博利珠單抗(pembrolizumab) 用於接受過鉑類化療後復發或轉移的頭頸部鱗狀細胞癌（R/M HNSCC）患者之安全性、耐受性與初步療效。
- 臨床試驗發起單位：台北榮民總醫院與林口長庚紀念醫院
- 主要研究者：張牧新醫師和謝佳訓醫師
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HCB101聯合治療機制
HCB101是一款經AI結構建模與10⁸種不同SIRPα變體的噬菌體展示庫篩選所開發的SIRPα融合蛋白。經特殊設計的HCB101能有效篩選出阻斷CD47-SIRPα的「別吃我」訊號，以增強巨噬細胞吞噬作用及重新活化適應性免疫，同時維持良好的安全性。前臨床數據指出，CD47阻斷劑可與免疫檢查點抑制劑（ICI）協同作用，有助於重塑腫瘤微環境並克服當前面對的免疫治療抗藥性。
- HCB101 + 帕博利珠單抗（pembrolizumab）
復發／轉移性頭頸癌具有高度免疫抑制性腫瘤微環境，PD-1抑制劑（如pembrolizumab）整體反應率僅約20%，臨床受限於抗原呈現障礙、T細胞耗竭、免疫抑制性髓系細胞浸潤及檢查點阻斷抗藥性。HCB101透過促進巨噬細胞活化、樹突狀細胞成熟與腫瘤特異性T 細胞浸潤，並將巨噬細胞表型從免疫抑制型M2轉為促發炎型M1，有望增強pembrolizumab的抗腫瘤活性。前臨床研究（如MOC1、ROC1小鼠模型）顯示，CD47與PD-1/PD-L1雙重阻斷能帶來更明顯腫瘤抑制與存活益處（Wu 等人，Oncoimmunology 2018）。鑒於帕博利珠單抗在HNSCC治療中的既有地位，以及PD-1阻斷可能誘導CD47表現上調的新興證據，HCB101 + 帕博利珠單抗的聯合策略可同時針對先天與適應性抗藥機制。此雙重路徑阻斷有潛力活化耗竭 T 細胞、提高反應深度，並將「冷腫瘤」轉化為「熱腫瘤」，為缺乏治療選擇的病人帶來希望。
「本次研究者發起的臨床試驗 (IIT) 提供了在免疫冷腫瘤如頭頸癌中，探索CD47與PD-1雙重阻斷療法協同效應的重要機會」，台北榮民總醫院主要研究者張牧新醫師表示。「透過針對先天與適應性抗藥性，我們希望此策略可帶來更持久的抗腫瘤反應，造福臨床病人。」
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關於HCB101：差異化的CD47-SIRPα免疫檢查點阻斷療法
HCB101是一款潛在同類最佳的Fc-融合SIRPα變體，專為優化免疫反應的活化，同時降低血液毒性而設計。與傳統CD47單株抗體不同，HCB101具備高選擇性的腫瘤靶向結合能力，同時降低紅血球(RBC)結合，減少貧血及血小板減少等副作用，展現出卓越的安全性優勢。
HCB101 的關鍵優勢
-卓越安全性：HCB101可顯著減少RBC消耗及血液毒性，相較於傳統CD47靶向療法更具耐受性。-協同增強免疫活性：HCB101強化ADCP作用，促進先天性免疫與適應性免疫聯合作用，產生更持久的抗腫瘤免疫反應。
-廣泛腫瘤適應性：HCB101在78多種CDX和PDX前臨床模型中已展現對多種實體瘤及血液惡性腫瘤的治療潛力。
HCB101目前正在多項臨床試驗中進行評估，包括：
- HCB101-101(NCT05892718)：一項1期開放式設計、多區域、多中心、劑量探索性(dose-finding)的首次人體(first-in-human)單藥臨床試驗，適用於晚期實體瘤或復發/難治性非霍奇金淋巴瘤(non-Hodgkin lymphomas, NHL)患者。
- HCB101-201(NCT06771622)：一項1b/2a期開放式設計、多區域、多中心臨床試驗，評估HCB101聯合標準治療(standard-of-care, SOC)用於晚期實體瘤的療效與安全性。
- HCB101-IIT-CRC-202401：一項開放式設計、劑量遞增(dose-escalation)及劑量擴展 (dose-expansion)的研究者發起臨床試驗(investigator-initiated trial, IIT)，評估HCB101聯合西妥昔單抗(cetuximab)或貝伐珠單抗(bevacizumab)及化療(FOLFOX或FOLFIRI)在RAS/BRAF野生型(wild-type)晚期或轉移性結直腸癌(colorectal cancer, CRC)中的安全性與初步療效。
- HCB101-IIT-HNSCC-202401：一項非隨機、開放標籤、劑量遞增及劑量擴展的研究者發起臨床試驗(investigator-initiated trial, IIT)，評估HCB101聯合帕博利珠單抗用於鉑類難治的復發／轉移性頭頸癌中的安全性與療效。
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關於漢康生技(HanchorBio)
漢康生技(HanchorBio)總部設於臺北、上海及美國舊金山灣區，是一家專注於腫瘤免疫治療(Immuno-Oncology)的全球生物技術公司。公司由擁有豐富經驗的製藥產業專家帶領，在生物藥發現與全球開發方面具有卓越成功的記錄，致力於重塑癌症治療格局。漢康生技致力於重新啟動人體免疫系統，以對抗惡性疾病。公司自主開發的Fc-基因工程多功能生物藥平臺(FBDB™, Fc-Based Designer Biologics)，能夠構建具備多重靶點機制的創新生物藥，通過先天性免疫與適應性免疫的協同調控，克服當前PD-1/PD-L1免疫療法的局限性。該技術平臺已在多種體內腫瘤動物模型中成功驗證概念(Proof-of-Concept, PoC)，展現出突破性的免疫調節潛力。通過研發創新多功能分子結構，並持續優化生產製程與CMC(化學、製造與管制)開發，漢康生技致力於開發突破性的創新療法，為尚未被滿足的臨床需求提供解決方案。