Innovent Dosed First Participant in Phase 3 Clinical Study of IBI354 (Novel HER2 ADC) for Platinum-resistant Ovarian Cancer

Innovent Dosed First Participant in Phase 3 Clinical Study of IBI354 (Novel HER2 ADC) for Platinum-resistant Ovarian Cancer

SAN FRANCISCO and SUZHOU, China, March 24, 2025 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, announces that the first participant has been successfully dosed with IBI354 (HER2 Monoclonal Antibody-Camptothecin Derivative Conjugate, HER2 ADC) in a randomized, controlled, multicenter Phase 3 clinical trial (HeriCare-Ovarian01), for platinum-resistant ovarian cancer (PROC) with HER2 expression.

HeriCare-Ovarian01 is the first Phase 3 clinical trial (NCT06834672) in China to investigate PROC with HER2 expression (IHC 1+, 2+ or 3+). The study will evaluate the safety and efficacy of IBI354, compared with investigator's choice of chemotherapy for PROC with HER2 expression. The primary endpoints are progression-free survival (PFS) and overall survival (OS).

Previously, in a multicenter Phase 1/2 study in participants with advanced solid tumors, a total of 87 participants with platinum-resistant ovarian cancer were enrolled and were treated with 6-12 mg/kg doses of IBI354. 67 (77.0%) participants had previously received at least 3 anti-tumor regimens.

• As of July 24, 2024, the overall objective response rate (ORR) was 40.2% and the disease control rate (DCR) was 81.6%.
• Among them, ORR reached 52.5% and DCR reached 90.0% in 40 ovarian cancer participants treated with 12mg/kg Q3W
• ORR reached 55.6% and DCR reached 88.9% in 27 subjects with HER2 IHC 1+ (12mg/kg Q3W dose group).
• The median follow-up time of 12mg/kg Q3W dose group was 6.5 months as of the cut-off date, and progression-free survival (PFS) and duration of response (DoR) were not mature. The data was presented at the ESMO conference.

In the phase 1/2 clinical study (n=368), IBI354 demonstrated an excellent safety profile. 

• No DLT was occurred up to 18mg/kg dose group.
• The overall incidence of grade 3 or higher treatment-related adverse events (TRAEs) was 21.5%, the incidence of TRAEs leading to dose interruption was 12.2%, the incidence of TRAEs leading to dose reduction was 2.4%, the overall incidence of TRAEs leading to discontinuation was 1.6%, and no TRAE leading to death reported.
• The most common TRAEs are nausea, white blood cell count decreased, and anemia. The incidence of interstitial lung disease was only 1.6%, all were grade 1.

The Principal Investigator of the HeriCare-Ovarian01 study, Prof. Qi Zhou from Chongqing University Cancer Hospital, stated, "Prolonging PFS and OS of PROC is an urgent unmet medical need. Ovarian cancer is characterized by a pattern of frequent recurrence, which ultimately leads to platinum resistance. Non-platinum monotherapy chemotherapy remains the primary treatment option at this stage, but its limited efficacy is a major contributor to the high mortality rate associated with ovarian cancer. As a fully-validated target, HER2-targeted therapy has proven effective in breast and gastric cancers. IBI354, as a innovative conjugate of anti-HER2 monoclonal antibody and camptothecin derivative, has shown good anti-tumor activity in PROC with HER2 expression in the previous study. Especially in the population with low HER2 expression (IHC 1+), the efficacy of IBI354 is comparable to that in the population with higher HER2 expression. At the same time, IBI354 has an excellent safety profile, showing a very low risk of common or concerned toxicities of other antibody-drug conjugates (ADCs), such as interstitial lung disease, fatigue, diarrhea, hair loss, eye toxicity, etc. I look forward to positive results from the HeriCare-Ovarian01 study. It is hoped that IBI354 may provide survival benefits to the PROC patients with varying levels of HER2 expression."

The Principal Collaborating Investigator of the study from Zhejiang Cancer Hospital, Prof. Tao Zhu, stated: "We are pleased to complete the first patient enrollment for the HeriCare-Ovarian01 study at our site. Although ovarian cancer ranks third among gynecologic malignancies in incidence, behind cervical and endometrial cancers, its mortality rate exceeds the combined total of the latter two, making it the deadliest gynecologic cancer and a severe threat to women's health. As an anti-HER2 ADC, preliminary findings from IBI354 have demonstrated encouraging objective response rates (ORR) and disease control rates (DCR) in PROC. Furthermore, IBI354 exhibits a superior clinical safety profile and treatment tolerability compared to other ADCs. Current clinical data suggest promising development prospects for IBI354 in PROC. We are hopeful that IBI354 will achieve success in the HeriCare-Ovarian01 study, offering new therapeutic options for this patient population."

Dr. Zhou Hui, Senior Vice President of Innovent, stated, "I'm pleased that the Phase III clinical study of IBI354 in HER2-expressing PROC has completed the first participant dosing. I look forward to positive results for IBI354 to provide a better treatment option for patients with HER2-expressing PROC. ADC is one of the core technology areas of Innovent's strategic layout. We combine the world's leading antibody engineering and multiple sets of differentiated linker-payload technologies to create a highly competitive and innovative TOPO1i ADC technology platform SoloTx^®. IBI354 has demonstrated excellent safety and efficacy data in the previous study, which fully proves the value and the development strength of Innovent ADC platform. We will deeply layout the ADC and immunotherapy areas, focusing on the next generation of innovation, committed to bring better benefits to cancer patients."

About Ovarian Cancer

OC is one of the leading causes of death among gynecological cancers. According to the International Agency for Research on Cancer, there will be about 324,000 new cases of ovarian cancer worldwide in 2022, and about 206,000 deaths^[1]. About 61,000 new cases and 33,000 deaths were reported in China^[2]. A higher mortality/morbidity ratio suggests a shorter survival time. Platinum-containing chemotherapy is the first choice for systemic treatment of advanced ovarian cancer. About 70% of patients with platinum-sensitive ovarian cancer will relapse after receiving platinum-containing chemotherapy and eventually develop platinum resistance^[3]. There is a lack of effective treatment for platinum-resistant cancer patients. The existing evidence is non-platinum-single drug chemotherapy with or without anti-angiogenic therapy, with ORR only about 4-13.2% and median overall survival (OS) only about 10.9-14 months^[4-8]. There is a urgent unmet medical need for PROC, and it is recommended that these patients participate in clinical trials in Chinese and foreign guidelines.It has been reported that about 38% of ovarian cancer patients have HER2 expression^[9]. There are currently no anti-HER2 treatments approved for HER2-overexpressed ovarian cancer in China.

About IBI354

IBI354 is an innovative HER2-targeted antibody–drug conjugate developed using Innovent's proprietary novel topoisomerase inhibitor platform. Based on this platform, Innovent is promoting clinical trial studies multiple self-developed ADC molecules, which have shown promising safety and efficacy signals.

With a drug-to-antibody ratio (DAR) of 8, IBI354 delivers a high payload of effective drugs to tumors. 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. IBI354 has demonstrated remarkable anti-tumor activity in various tumor-bearing mice models, particularly in those resistant to HER2-targeted therapies and in metastatic tumors.

Starting from the urgent clinical needs, in addition to the phase III study (HeriCare-Ovarian01) already initiated in PROC, Innovent will develop IBI354 in multiple solid tumor indications.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement:

1) Innovent does not recommend the use of any unapproved drug (s)/indication (s).

2) Ramucirumab (Cyramza) and Selpercatinib (Retsevmo) and Pirtobrutinib (Jaypirca) were developed by Eli Lilly and Company.

Disclaimer: Innovent does not recommend any off-label usage.

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

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