Innovent Initiates Phase 3 Trial of IBI354 HER2 ADC for First-Line HER2-Positive Breast Cancer Treatment
核心洞察
Innovent Biologics (搜索) has dosed the first participant in the pivotal Phase 3 HeriCare-Breast01 trial evaluating IBI354, a novel HER2 (搜索)-targeted antibody-drug conjugate, as first-line treatment for unresectable locally advanced or metastatic HER2-positive breast cancer (搜索).
The multicenter, randomized, open-label study compares IBI354 with or without pertuzumab against the current standard-of-care THP regimen, with progression-free survival as the primary endpoint.
Previous Phase 1/2 data showed IBI354 achieved a 72.4% objective response rate and 89.7% disease control rate in breast cancer (搜索) patients at the 9mg/kg dose, with a favorable safety profile including only 1.2% incidence of interstitial lung disease (搜索).
Innovent Biologics (搜索) has successfully dosed the first participant in its pivotal Phase 3 clinical study HeriCare-Breast01, evaluating the company's novel HER2 (搜索)-targeted antibody-drug conjugate IBI354 as a first-line treatment for patients with unresectable locally advanced or metastatic HER2-positive breast cancer (搜索). The milestone marks a significant advancement in the development of next-generation ADC therapies designed to deliver "high potency and low-toxicity" treatment options.
Phase 3 Trial Design and Objectives
The HeriCare-Breast01 study (NCT07377643 (搜索)) is a multicenter, randomized, open-label, active-controlled trial designed to evaluate the safety and efficacy of IBI354, with or without pertuzumab, compared with the current standard-of-care regimen of paclitaxel plus trastuzumab and pertuzumab (THP). The study's primary endpoint is progression-free survival (PFS).
This Phase 3 trial represents one of two pivotal studies for IBI354, alongside the ongoing HeriCare-Ovarian01 trial, positioning the drug candidate to potentially address significant unmet medical needs in HER2 (搜索)-positive cancers.
Promising Early-Stage Clinical Results
IBI354 has demonstrated compelling efficacy signals in previous clinical studies. In a multicenter Phase 1/2 study involving participants with advanced solid tumors, 88 participants with HER2-positive breast cancer (搜索) were enrolled with a median of 4 prior treatment lines and treated with 6-15 mg/kg doses of IBI354.
As of March 24, 2025, the overall confirmed objective response rate (cORR) reached 59.1% with a disease control rate (DCR) of 90.9%. Among the 29 breast cancer (搜索) participants treated with the 9mg/kg every three weeks (Q3W) dosing regimen, the objective response rate reached 72.4% and the disease control rate achieved 89.7%.
The median follow-up time for the 9mg/kg Q3W dose group was 13.6 months, with progression-free survival reaching 14.1 months (95% CI: 8.3, NC). These data were presented at ASCO 2025.
Superior Safety Profile
IBI354 demonstrated an excellent safety profile in the Phase 1/2 clinical study involving 368 participants. No dose-limiting toxicities (DLT) occurred up to the 18mg/kg dose group. In the 9mg/kg Q3W dose group, the overall incidence of grade 3 or higher treatment-related adverse events (TRAEs) was 21.0%.
The incidence of TRAEs leading to dose interruption was 9.9%, dose reduction was 1.2%, and treatment discontinuation was 1.2%, with no TRAE-related deaths reported. The most common treatment-related adverse events included decreased white blood cell count, nausea, and anemia. Notably, the incidence of interstitial lung disease (搜索) was only 1.2%, with all cases being grade 1.
Expert Perspectives on Clinical Significance
Binghe Xu, academician of the Chinese Academy of Engineering from Cancer Hospital Chinese Academy of Medical Sciences (搜索) and Principal Investigator of the HeriCare-Breast01 study, emphasized the clinical need addressed by IBI354. "Although first-line treatment for HER2 (搜索)-positive advanced breast cancer (搜索) has improved substantially—with the THP regimen delivering durable responses for many patients—important clinical challenges remain. These include treatment discontinuation driven by toxicity and limited tolerability of currently available ADCs, particularly among older patients and those with comorbid conditions," Xu stated.
He highlighted IBI354's potential advantages: "As a next-generation HER2 (搜索)-targeted ADC, IBI354 has shown compelling antitumor activity in Phase 1/1b studies, achieving class-leading ORR and DCR, alongside a notably favorable safety profile. In particular, IBI354 has demonstrated reduced incidence of key adverse events such as interstitial lung disease (搜索) (ILD), peripheral neuropathy, and neutropenia."
Advanced ADC Technology Platform
IBI354 is developed using Innovent's proprietary SoloTx® ADC platform, featuring advanced antibody engineering and differentiated linker-payload technologies. The drug candidate has a drug-to-antibody ratio (DAR) of 8, enabling high payload delivery to tumors.
Dr. Zhou Hui, Chief R&D Officer (Oncology) of Innovent, noted the technological advantages: "The highly hydrophilic linker design contributes to its excellent biophysical and pharmacokinetic (PK) properties, while the hydrophobic payload enhances its bystander effect, targeting adjacent antigen-low or negative tumor cells. IBI354 exhibits extremely low exposure of free toxin in circulation and has an ideal safety profile based on pre-clinical and clinical studies."
Addressing Unmet Medical Need
Breast cancer (搜索) affects approximately 1.3 million women annually worldwide, with about 30% developing locally advanced or metastatic disease. HER2-positive breast cancer (搜索) represents approximately 20% of all breast cancer cases. Previous studies have demonstrated that HER2 (搜索) gene overexpression plays a significant role in invasive breast cancer development and is associated with increased recurrence rates and poor prognosis.
Currently, no ADC targeting HER2 (搜索) has been fully approved for first-line treatment of advanced breast cancer (搜索) in China, highlighting the urgent need for new therapeutic options to improve patient prognosis.
Future Development Plans
Beyond the ongoing Phase 3 studies in breast cancer (搜索) and ovarian cancer, Innovent plans to explore IBI354 in multiple solid tumor indications. The company continues to advance innovation in next-generation IO+ADC combinations, maintaining its commitment to delivering improved therapeutic outcomes for cancer patients.
The successful initiation of the HeriCare-Breast01 trial represents a significant milestone in Innovent's ADC pipeline development and the potential advancement of precision oncology treatments for HER2-positive breast cancer (搜索) patients.