HCB101, Novel Fusion Protein, Earns FDA Orphan Drug Status in Gastric Cancer

HCB101, a novel Fc-based anti-SIRPα-CD47 fusion protein, has received orphan drug designation (ODD) from the FDA for the treatment of gastric cancer.¹ The designation encompasses gastric cancer broadly, including both HER2 subtypes of advanced gastric adenocarcinoma.

The ODD program provides incentives to sponsors developing drugs for rare diseases, defined as those affecting fewer than 200,000 people in the US. These incentives include 7 years of marketing exclusivity upon regulatory approval, exemptions from user fees under the Prescription Drug User Fee Act, and federal tax credits for qualified clinical trial expenses. While the designation facilitates the development process, the safety and efficacy of HCB101 must still be established through rigorous clinical investigation before it can be considered for full approval.

"The FDA's decision reflects the seriousness of gastric cancer and the clinical rationale underlying HCB101's development. HCB101's IgG4-based SIRPα-Fc design was intentionally selected to support repeated dosing and combination strategies as an innate immune checkpoint backbone in solid tumors,” said Alvin Luk, PhD, MBA, chief medical officer of agent developer HanchorBio, in a news release.¹ “In a second-line gastric cancer setting, where standard regimens offer limited durability, the depth of tumor shrinkage and consistency of response observed to date, while remaining compatible with standard ramucirumab [Cyramza]-paclitaxel administration, support the continued global advancement of HCB101 for patients with significant unmet need."

Mechanism of Action

HCB101 is designed to target the CD47–SIRPα axis, a critical immune checkpoint often exploited by solid and hematologic tumors to evade surveillance. By acting as a decoy receptor, HCB101 blocks the CD47-SIRPα interaction, effectively neutralizing the inhibitory signal and enabling the innate immune system to identify and eliminate malignant cells.

A primary challenge in the development of CD47-targeted therapies has been the ubiquitous expression of CD47 on healthy cells, particularly erythrocytes and platelets. Many first-generation CD47 monoclonal antibodies have been associated with significant hematologic toxicities, including severe anemia and thrombocytopenia, necessitated by the "sink effect" where the drug binds extensively to red blood cells. HCB101 is engineered to minimize these off-target effects.

Preclinical models have demonstrated that HCB101 has a high affinity to CD47, induces macrophage-mediated phagocytosis of tumor cells without affecting red blood cells, significantly inhibited tumor growth, and increased the M1/M2 macrophage ratio in the tumor microenvironment.² This profile suggests a reduced risk of treatment-limiting hematologic adverse events (AEs) compared with earlier agents in this class.

Clinical Development Status and Early Data

The clinical utility of HCB101 is currently being evaluated in a phase 1b/2a trial (NCT06771622) in China. The trial is designed as a dose-escalation and dose-expansion study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of HCB101 in combination with multiple standard or approved anticancer therapies in patients with advanced solid tumors.³ The study is estimated to complete by 2029.

Patients have been enrolled across various cohorts according to tumor type and prior treatment lines. Tumor types represented include gastric cancer, colorectal cancer, hepatocellular carcinoma, triple-negative breast cancer, head and neck squamous cell carcinoma, ovarian cancer, and extensive-stage small cell lung cancer.

Another ongoing phase 1 study (NCT05892718) is also evaluating HCB101 in advanced solid tumors and hematologic malignancies, with a focus on relapsed/refractory non-Hodgkin lymphoma. Interim data from this trial, presented at the 2025 American Society of Clinical Oncology Annual Meeting, showed that the agent was well-tolerated among 32 treated patients, with primarily grade 1 or 2 anemia (17%) as the most common treatment-related AEs.⁴ Additionally, among 21 efficacy-evaluable patients, 29% showed stable disease, indicating early antitumor activity in a heavily pretreated population.

REFERENCES

1. HanchorBio receives U.S. Food and Drug Administration orphan drug designation for HCB101 in gastric cancer. News release. HanchorBio. February 13, 2026. Accessed February 16, 2026. https://tinyurl.com/57fmjrkv

2. Wang JT, Tseng CL, Teng HF, et al. HCB101: a novel potent ligand-trap Fc-fusion protein targeting the CD47-SIRPα pathway with high safety and preclinical efficacy for hematological and solid tumors. J Hematol Oncol. 2025;18(1):87. Published 2025 Oct 23. doi:10.1186/s13045-025-01742-x

3. Safety and efficacy of HCB101 in combination with multiple agents in patients with advanced solid tumors. ClinicalTrials.gov. Updated February 4, 2026. Accessed February 16, 2026. https://clinicaltrials.gov/study/NCT06771622

4. Yan L, Sun D, Zhang V, et al. Phase 1 trial of HCB101, a novel Fc-based anti-SIRPα-CD47 fusion protein, in subjects with advanced cancers. J Clin Oncol. 2025;43(16_suppl):2584-2584. doi:10.1200/jco.2025.43.16_suppl.2584