Sacituzumab Biosimilar: Advancing Trop-2-Targeted Cancer Therapy

Sacituzumab govitecan is an innovative antibody-drug conjugate (ADC) targeting Trop-2, a transmembrane glycoprotein overexpressed in many epithelial cancers. By selectively delivering a cytotoxic payload to Trop-2-positive cancer cells, Sacituzumab has demonstrated significant efficacy in difficult-to-treat cancers such as triple-negative breast cancer (TNBC). The biosimilar HDBS0023 replicates the therapeutic benefits of the original biologic while offering a more cost-effective solution for patients.

This article explores the mechanism of action, clinical applications, and benefits of HDBS0023 in oncology.

What is Trop-2?

Trop-2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein involved in:

• Tumor Growth and Survival: Trop-2 signaling promotes cancer cell proliferation and invasion.
• Overexpression in Cancers: Found in various solid tumors, including TNBC, urothelial carcinoma, and lung adenocarcinoma.

Why Target Trop-2?

• Tumor-Specific Expression: High expression in cancer cells with minimal presence in normal tissues.
• Predictive Biomarker: Trop-2 overexpression correlates with poor prognosis, making it an attractive therapeutic target.

Features of HDBS0023

HDBS0023 is a biosimilar to Sacituzumab govitecan, designed to deliver equivalent efficacy and safety at a lower cost.

• Target: Trop-2 on cancer cells.
• Mechanism: Delivers the cytotoxic payload SN-38 selectively to Trop-2-positive tumors.
• Affordability: Reduces the financial burden of ADC therapy, improving access to advanced treatment.

HDBS0023 mirrors the efficacy of Sacituzumab govitecan in treating Trop-2-positive cancers, including:

Triple-Negative Breast Cancer (TNBC)

• Approved Indication: Effective in relapsed/refractory TNBC, providing significant survival benefits.
• Combination Therapy: Being investigated alongside immune checkpoint inhibitors for enhanced efficacy.

Urothelial Carcinoma

• Second-Line Therapy: Demonstrates efficacy in advanced or metastatic urothelial carcinoma after platinum-based chemotherapy or immune checkpoint inhibitors.

Non-Small Cell Lung Cancer (NSCLC)

• Targets Trop-2-positive lung adenocarcinomas, offering a promising option for refractory cases.

Tumor-Specific Cytotoxicity

HDBS0023 selectively delivers SN-38 to Trop-2-positive tumors, minimizing off-target effects.

Cost-Effective Access

HDBS0023 makes Trop-2-targeted therapy more affordable, increasing accessibility in resource-limited settings.

Broad Therapeutic Potential

HDBS0023 is effective across a range of Trop-2-positive cancers and demonstrates synergistic effects in combination therapies.

Adverse Effects

• Hematologic Toxicity: Common side effects include neutropenia and anemia, requiring supportive care.
• Gastrointestinal Toxicity: Diarrhea is a known side effect of SN-38, manageable with dose adjustments.

Resistance Mechanisms

• Tumors may develop resistance by downregulating Trop-2 or increasing drug efflux. Combination therapies can mitigate this risk.

Expanded Indications

• Investigating HDBS0023 in additional Trop-2-positive cancers, such as colorectal and ovarian cancers.

Combination Therapies

• Checkpoint Inhibitors: Combining HDBS0023 with PD-1/PD-L1 inhibitors for enhanced immune-mediated clearance of Trop-2-positive tumors.
• Chemotherapy: Exploring synergies with standard cytotoxic agents to improve overall response rates.

The Sacituzumab biosimilar HDBS0023 represents a significant advancement in targeted cancer therapy. By selectively targeting Trop-2, HDBS0023 delivers potent anti-tumor effects in refractory and advanced cancers such as TNBC and urothelial carcinoma. As a cost-effective alternative, it expands access to innovative therapies, offering hope to patients worldwide.

1. Bardia, A., et al., 2021. Sacituzumab govitecan in metastatic triple-negative breast cancer. NEJM, 384(16), pp.1529-1541.
2. ClinicalTrials.gov, 2023. Studies on Sacituzumab govitecan and biosimilar HDBS0023. Available at www.clinicaltrials.gov.
3. Goldenberg, D.M., et al., 2018. Trop-2 as a therapeutic target in cancer: Development of antibody-drug conjugates. Oncotarget, 9(48), pp.28989-29006.
4. European Medicines Agency (EMA), 2023. Guidelines on biosimilar ADCs. Available at www.ema.europa.eu.
5. Tagawa, S.T., et al., 2021. Trop-2 targeting in urothelial carcinoma: Mechanistic insights and clinical advances. Cancer Immunology Research, 9(7), pp.805-816.