Innovent Biologics advances IBI354 into Phase 3 trial for HER2-expressing platinum-resistant ovarian cancer

Innovent Biologics has taken a significant step in the fight against ovarian cancer by initiating a Phase 3 clinical trial for IBI354, a novel HER2-targeted antibody-drug conjugate (ADC). The trial, named HeriCare-Ovarian01, marks the first large-scale study in China evaluating a HER2-expressing therapy specifically for platinum-resistant ovarian cancer (PROC). With the first participant successfully dosed, this study could pave the way for a new treatment paradigm in one of the most lethal gynecologic malignancies.

The development of IBI354 aligns with a growing scientific focus on HER2-targeted therapies, which have already demonstrated success in breast and gastric cancers. Ovarian cancer, known for its high recurrence rate and resistance to conventional chemotherapy, represents an urgent area for innovation. While platinum-based chemotherapy remains the standard for newly diagnosed cases, PROC patients face limited treatment options, often resulting in poor survival outcomes. The introduction of HER2-targeted ADCs like IBI354 could redefine how advanced ovarian cancer is managed.

How Does the HeriCare-Ovarian01 Study Aim to Improve Treatment for PROC?

HeriCare-Ovarian01, a randomized, controlled, multicenter Phase 3 clinical trial, is investigating IBI354’s efficacy and safety compared to investigator-chosen chemotherapy in PROC patients with HER2 expression (IHC 1+, 2+, or 3+). The study’s primary endpoints include progression-free survival (PFS) and overall survival (OS)—two critical measures in assessing the impact of new cancer treatments.

This trial builds on promising results from earlier Phase 1/2 studies, where IBI354 demonstrated significant anti-tumor activity in PROC patients. Data from these studies revealed that 40.2% of participants showed an objective response rate (ORR), while 81.6% achieved disease control (DCR). In a subset of patients receiving a 12 mg/kg Q3W dose, ORR climbed to 52.5%, with DCR reaching 90.0%. Notably, even in patients with low HER2 expression (IHC 1+), response rates remained high, with 55.6% achieving ORR and 88.9% showing disease control.

Innovent’s approach with IBI354 offers a potential alternative to conventional non-platinum chemotherapy, which currently provides limited benefits for PROC patients. Existing treatments, such as single-agent chemotherapy with or without anti-angiogenic therapy, deliver poor ORR outcomes ranging between 4% and 13.2%, with median OS of just 10.9 to 14 months. By targeting HER2-expressing cancer cells with a highly potent payload, IBI354 aims to extend survival and improve treatment responses in a patient population with few effective options.

What Sets IBI354 Apart from Other HER2-Targeted Therapies?

IBI354 is designed using Innovent’s proprietary topoisomerase inhibitor platform, incorporating an anti-HER2 monoclonal antibody conjugated with a camptothecin derivative. This mechanism allows for the targeted delivery of a cytotoxic agent directly to cancer cells expressing HER2, enhancing treatment efficacy while minimizing systemic toxicity.

Unlike earlier HER2-targeted therapies, which were predominantly developed for breast and gastric cancers, IBI354 is among the first ADCs specifically evaluated for HER2-expressing ovarian cancer. With a drug-to-antibody ratio (DAR) of 8, IBI354 delivers a higher therapeutic payload than many traditional ADCs, potentially increasing its tumor-killing potency.

Another key advantage of IBI354 is its highly hydrophilic linker design, which contributes to enhanced pharmacokinetic properties and stability in circulation. Additionally, its hydrophobic payload enhances the bystander effect, meaning that IBI354 can also target neighboring cancer cells with low or negative HER2 expression, expanding its therapeutic reach beyond patients with high HER2 levels.

What Do Experts Say About IBI354’s Potential in Ovarian Cancer?

Leading oncology researchers have expressed optimism about IBI354’s potential impact. Professor Qi Zhou from Chongqing University Cancer Hospital, the principal investigator of HeriCare-Ovarian01, highlighted the urgent need for new treatments in PROC, emphasizing that HER2-targeted therapy has already proven effective in other cancers. He noted that IBI354’s ability to deliver strong efficacy even in patients with low HER2 expression could make it a game-changer in PROC management.

Professor Tao Zhu from Zhejiang Cancer Hospital, a principal collaborating investigator, underscored the severity of ovarian cancer’s mortality rate, noting that despite being the third most common gynecologic malignancy, it accounts for more deaths than cervical and endometrial cancers combined. He described IBI354 as a promising addition to the arsenal of available treatments, citing its high ORR, DCR, and superior safety profile compared to other ADCs.

How Does IBI354’s Safety Profile Compare to Other Treatments?

One of the key findings from earlier trials was IBI354’s excellent safety profile, distinguishing it from many existing cancer therapies. In a Phase 1/2 study involving 368 participants, IBI354 demonstrated:

• No dose-limiting toxicities (DLTs) up to 18 mg/kg
• A low incidence of severe (Grade 3 or higher) treatment-related adverse events (TRAEs) at 21.5%
• Minimal risk of serious side effects commonly associated with ADCs, such as interstitial lung disease (only 1.6%)
• A very low discontinuation rate (1.6%) due to TRAEs

This favorable safety profile suggests that IBI354 could provide a more tolerable treatment option for PROC patients, many of whom have undergone multiple lines of therapy and are particularly vulnerable to adverse effects.

What Does the Future Hold for IBI354 and Innovent’s ADC Pipeline?

The initiation of HeriCare-Ovarian01 represents a critical milestone for Innovent Biologics, reinforcing its commitment to advancing antibody-drug conjugates and immunotherapies. Dr. Zhou Hui, Senior Vice President of Innovent, highlighted the company’s strategic focus on ADC development, noting that IBI354 is part of a broader effort to create next-generation therapies that improve cancer treatment outcomes.

In addition to ovarian cancer, Innovent is exploring IBI354 for multiple solid tumor indications, aiming to expand its use beyond gynecologic malignancies. The company has also built a highly competitive ADC platform, SoloTx®, combining advanced antibody engineering with differentiated linker-payload technologies to enhance treatment precision.

If the HeriCare-Ovarian01 trial confirms IBI354’s efficacy and safety, Innovent could position itself as a key player in the growing HER2-targeted therapy market, potentially seeking regulatory approval for widespread clinical use. Given the lack of approved HER2 therapies for ovarian cancer in China, a successful outcome could fill a critical gap in current treatment strategies.

As research progresses, the oncology community will closely watch the long-term survival data and overall impact of IBI354. Should this innovative ADC demonstrate sustained benefits, it may well become a cornerstone treatment for PROC patients, offering new hope in a field where breakthroughs are desperately needed.