Report on IBI354 Treatment for HER2-Positive Breast Cancer and Its Alignment with Sustainable Development Goals (SDGs)

Introduction

Recent findings from a phase 1 clinical trial (NCT05636215) have demonstrated that the novel antibody-drug conjugate (ADC) IBI354 is both safe and effective in treating patients with pretreated HER2-positive advanced breast cancer. These results were presented at the 2025 ASCO Annual Meeting. The study’s outcomes contribute significantly to the Sustainable Development Goals (SDGs), particularly SDG 3 (Good Health and Well-being) by advancing cancer treatment options.

Clinical Efficacy of IBI354

1. Overall Response Rate (ORR): Among 88 evaluable patients with HER2-positive breast cancer, the ORR was 59.1% (95% CI, 48.1%-69.5%), including:
   • Complete response rate: 4.5%
   • Partial response rate: 54.5%
2. Disease Control Rate (DCR): 90.9% (95% CI, 82.9%-96.0%) of patients achieved disease control.
3. Stable and Progressive Disease Rates: Stable disease (SD) was observed in 31.8%, and progressive disease (PD) in 9.1% of patients.

Subgroup Analysis at 9 mg/kg Dose

• In 29 patients treated with 9 mg/kg every 3 weeks, the ORR was 72.4% (95% CI, 52.8%-87.3%), consisting exclusively of partial responses.
• Stable disease and progressive disease rates were 17.2% and 10.3%, respectively.
• Disease control rate was 89.7% (95% CI, 72.6%-97.8%).

Safety Profile

• Among 368 patients in the safety population, any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.6% of patients.
• Grade 3 or higher TEAEs were reported in 39.1% of patients.
• Treatment-related adverse events (TRAEs) of any grade and grade 3 or higher occurred in 90.8% and 27.4% of patients, respectively.
• Serious adverse events (AEs) and treatment-related serious AEs were reported in 20.7% and 9.0% of patients, respectively.
• TEAEs led to treatment interruption (26.9%), dose reduction (2.7%), and discontinuation (1.9%).
• One patient (0.3%) died due to TEAEs; no deaths were attributed to TRAEs.
• Treatment-related interstitial lung disease was observed in 1.9% of patients.

These safety outcomes support SDG 3 by ensuring treatments are not only effective but also safe for patients, promoting well-being and reducing mortality from non-communicable diseases.

IBI354 Background and Phase 1 Study Design

IBI354 is an innovative ADC composed of trastuzumab (Herceptin) linked to a camptothecin derivative. Its mechanisms include:

• Selective antibody binding to tumor cells.
• Internalization and lysosomal degradation releasing a cytotoxic payload.
• Inhibition of topoisomerase 1 activity, inducing DNA damage and apoptosis.
• Bystander effect targeting neighboring cancer cells.

The global, multicenter phase 1 trial enrolled patients with advanced breast cancer and other HER2-expressing solid tumors who had progressed on or were intolerant to standard therapies. Eligibility required HER2 expression levels of IHC 2+/in situ hybridization+ or IHC 3+ for breast cancer patients. Doses ranged from 0.8 mg/kg to 18 mg/kg administered every 2 or 3 weeks.

Primary endpoint: Safety assessment.
Secondary endpoints: Overall response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Patient demographics included a median age of 53 years, predominantly female (98.9%), Asian ethnicity (100%), ECOG performance status 1 (75%), stage IV disease (97.7%), and majority with IHC 3+ HER2 expression (80.7%). Most patients had received at least three prior lines of therapy (73.9%).

Prior treatments included taxanes (96.6%), trastuzumab or biosimilars (100%), pertuzumab (37.5%), ado-trastuzumab emtansine (37.5%), and HER2 tyrosine kinase inhibitors (81.8%).

Additional Clinical Data

• Duration of response (DOR) data remain immature; however, the 12-month DOR rate was 61.2% (95% CI, 43.7%-74.8%).
• In the 9 mg/kg dose group, median progression-free survival (PFS) was 14.1 months (95% CI, 8.3 months to not calculable).
• Overall survival (OS) data are immature, with events reported in 3.4% of patients.

Alignment with Sustainable Development Goals (SDGs)

• SDG 3: Good Health and Well-being – The development of IBI354 advances cancer treatment, improving survival and quality of life for patients with HER2-positive breast cancer.
• SDG 9: Industry, Innovation, and Infrastructure – The innovative ADC technology exemplifies progress in medical research and pharmaceutical development.
• SDG 10: Reduced Inequalities – The global, multicenter nature of the trial promotes equitable access to cutting-edge therapies across diverse populations.
• SDG 17: Partnerships for the Goals – Collaboration among international research centers and healthcare institutions supports the achievement of health-related SDGs.

Conclusion

The phase 1 trial results for IBI354 demonstrate promising antitumor activity and a manageable safety profile in patients with HER2-positive advanced breast cancer. These findings contribute to the global effort to improve cancer care and align with multiple Sustainable Development Goals, particularly SDG 3, by fostering innovations that enhance health outcomes worldwide.

Reference

Lemech C, Sun Y, Nagrial A, et al. IBI354 (anti-HER2 antibody-drug conjugate [ADC]) in patients (pts) with HER2-positive breast cancer (BC) and other solid tumors: Updates from a phase 1 study. J Clin Oncol. 2025;43(suppl 16):1029. doi:10.1200/JCO.2025.43.16_suppl.1029

1. Sustainable Development Goals (SDGs) Addressed

1. SDG 3: Good Health and Well-being
   • The article focuses on the treatment of HER2-positive advanced breast cancer, highlighting medical research and clinical trials aimed at improving health outcomes.
   • It addresses issues related to cancer treatment safety, efficacy, and patient survival, which are central to ensuring healthy lives and promoting well-being.
2. SDG 9: Industry, Innovation and Infrastructure
   • The development and testing of the novel antibody-drug conjugate (IBI354) demonstrate innovation in pharmaceutical research and healthcare infrastructure.
3. SDG 10: Reduced Inequalities
   • The study involves a global, multicenter trial with patients from diverse backgrounds (e.g., Asian population), indicating efforts to reduce health inequalities by including varied demographics in clinical research.

2. Specific Targets Under the Identified SDGs

1. SDG 3: Good Health and Well-being
   • Target 3.4: By 2030, reduce by one third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.
   • Target 3.8: Achieve universal health coverage, including access to quality essential health-care services and access to safe, effective, quality, and affordable essential medicines and vaccines for all.
2. SDG 9: Industry, Innovation and Infrastructure
   • Target 9.5: Enhance scientific research, upgrade the technological capabilities of industrial sectors, including health-related industries.
3. SDG 10: Reduced Inequalities
   • Target 10.2: Empower and promote the social, economic and political inclusion of all, irrespective of age, sex, disability, race, ethnicity, origin, religion or economic or other status.

3. Indicators Mentioned or Implied in the Article

1. For SDG 3 (Good Health and Well-being):
   • Indicator 3.4.1: Mortality rate attributed to cardiovascular disease, cancer, diabetes or chronic respiratory disease. The article provides data on overall response rates (ORR), disease control rates (DCR), progression-free survival (PFS), and overall survival (OS) in breast cancer patients, which are key measures of treatment effectiveness and patient outcomes.
   • Indicator 3.8.1: Coverage of essential health services. The clinical trial data on safety profiles, treatment-emergent adverse effects (TEAEs), and treatment-related adverse events (TRAEs) reflect quality and safety of healthcare services and medicines.
2. For SDG 9 (Industry, Innovation and Infrastructure):
   • No direct indicator is mentioned, but the phase 1 clinical trial progress and innovation in drug development can be linked to indicators measuring research and development expenditure or number of new health technologies developed.
3. For SDG 10 (Reduced Inequalities):
   • No explicit indicators are mentioned, but inclusion of diverse patient populations in clinical trials can be linked to indicators measuring equality of access to health services.

4. Table of SDGs, Targets, and Indicators

Source: onclive.com