Innovent presented oral data at the 2024 European Society for Medical Oncology (ESMO) Congress in the treatment of IBI354, an anti-HER2 monoclonal antibody-camptothecin derivative conjugate (HER2 ADC), in the treatment of solid tumors such as advanced ovarian cancer and breast cancer

SAN FRANCISCO, United States and SUSU, China, Sept. 18, 2024 /PRNewswire/ -- Innovent Biologics Group (HKEX: 01801), a biopharmaceutical company dedicated to the development, production and marketing of innovative drugs in the fields of oncology, autoimmunity, metabolism, ophthalmology and other major diseases. Clinical data of IBI354, an anti-HER2 monoclonal antibody-camptothecin derivative conjugate, in the treatment of multiple advanced solid tumors were presented at the 2024 European Society for Medical Oncology (ESMO) Congress (study registration number: NCT05636215).

The data presented in this release are from a Phase 1/2 study to evaluate the safety, tolerability and preliminary efficacy of IBI354 in subjects with advanced solid tumors. A total of 368 subjects with advanced solid tumors received different doses of IBI354 monotherapy, including 178 subjects with breast cancer, 92 cases of ovarian cancer, 38 cases of colorectal cancer and 60 subjects with other tumors. Among them, 42.7% of the participants had been treated with five or more prior systemic treatment regimens. The results of the study showed that:

IBI354 monotherapy has demonstrated an excellent safety profile:

• Dose escalation to: 18mg, No DLT events occurred.
• The most common TRAEs are nausea, low white blood cell count, and anemia. The incidence of interstitial pneumonia is only 1.6%, and all of them are level 1.
• The overall incidence of tertiary and higher treatment-related adverse events (TRAEs) was 21.5%, the overall incidence of TRAEs leading to dose reduction was 2.4%, the overall incidence of TRAEs leading to permanent discontinuation was 1.6%, and there were no TRAEs resulting in death.

IBI354 has shown positive early efficacy signals in multiple cancer types:

• In platinum-resistant ovarian cancer (n=87, 6 ~12mg/kg IBI354 treatment), the overall objective response rate (ORR) was 40.2%, and the disease control rate (DCR) was 81.6%. thereinto at The ORR was 52.5% and the DCR was 90.0% in 40 ovarian cancer subjects treated with 12 mg/kg IBI354, and the ORR was 55.6% and the DCR was 88.9% in 27 subjects treated with HER2 IHC 1+. As of the data cut-off date, the median follow-up was 6.5 months, and progression-free survival (PFS) and duration of response (DoR) were not yet mature.
• HER2阳性乳腺癌中(n=59, 6~15mg/kg IBI354 治疗)， The ORR and DCR were 67.8% and 88.1%, respectively.
• In HER2-low breast cancer (n=67, 6~15mg/kg IBI354 treatment), the ORR and DCR were 41.8% and 82.1%, respectively. thereinto Twenty-six patients were treated with 12mg/kg IBI354, with an ORR of 61.5% and a DCR of 88.5%.
• Among the HER2-positive malignant tumors of the digestive system, a total of 35 subjects were treated with 6~15mg/kg IBI354, and the ORR and DCR were 57.1% and 91.4%, respectively. Of these, 26 were colorectal cancer subjects and 14 achieved objective remission (of these One HER2 IHC2+ FISH+ subject achieved a confirmed objective response ）， The ORR and DCR were 53.8% and 92.3%, respectively. As of press time, another 1 HER2-low expression (IHC2+ FISH-) subject was rated as having a confirmed objective remission.

Professor Zhou Qi, chief expert of the Gynecologic Cancer Center of the Affiliated Cancer Hospital of Chongqing University, was the principal investigator of the gynecological tumor cohort of the study

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"Approximately 70% of ovarian cancer patients relapse within three years of surgery and adjuvant platinum-containing therapy, and multiple recurrences eventually develop platinum resistance [1]. Patients with platinum-resistant cancer lack effective treatment, and the available evidence is that nonplatinum monotherapy or anti-angiogenic therapy has an ORR of only about 4 to 13.2 percent and a median overall survival (OS) of only about 10.9 to 14 months[2]-[3][4][5][6]. As a mature target, HER2 targeted therapy has been shown to have good efficacy in breast cancer and gastric cancer. IBI354, as an anti-HER2 monoclonal antibody-camptothecin derivative conjugate, demonstrated good anti-tumor activity in platinum-resistant ovarian cancer with HER2 expression 1+, and in our Phase I study, we showed a clinical benefit of 67.5% ORR, 88.9% DCR, and 39.0% PFS event in 12mg/kg Q3W, while a favorable safety profile of IBI354 was seen in the trial. Prolonging PFS and OS in platinum-resistant relapsed ovarian cancer is a clinical problem that needs to be solved urgently in gynecological tumors, and the research and development of antibody-drug conjugates in drug-resistant relapsed tumors has become a hot topic, and there is hope that the clinical efficacy of antibody-drug conjugates with low expression of HER2 is worthy of further clinical experimental research and exploration, which will bring benefits to more patients with platinum-resistant ovarian cancer. "

Melbourne, Australia Monash Health医院临床肿瘤中心Daphne Day博士

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"Breast cancer is the second most common malignancy in the world, with the highest incidence in women, and is one of the leading causes of death among women [7]. HER2 amplification or overexpression has been shown to play an important role in the development and progression of breast cancer, confirming the importance of targeted HER2 therapy. Preliminary results of IBI354 as an anti-HER2 monoclonal antibody-camptothecin derivative conjugate suggest that meaningful objective response rates and disease control rates were observed in HER2-positive and low-expression breast cancers. IBI354 also demonstrated excellent clinical safety and tolerability. The existing clinical data suggest that IBI354 has sufficient development prospects in the breast cancer population. "

Professor Shen Lin from Peking University Cancer Hospital

"Colorectal cancer has become the second most common malignant tumor in China after lung cancer, and the incidence and mortality rates are still increasing year by year [8]. HER2 targets also play an important role in the posterior treatment of colorectal cancer. Preliminary results of IBI354 as an anti-HER2 monoclonal antibody-camptothecin derivative conjugate suggest that positive efficacy has been observed in HER2-positive malignant cancers of the digestive system. Notably, IBI354 has also observed anti-tumor effects in HER2-low expression populations with relatively poor HER2-targeted therapy. IBI354 has also demonstrated a good clinical safety and tolerability in subjects with posterior colorectal cancer, supporting continued exploration and development in subjects with colorectal cancer. "

Dr. Hui Zhou, Senior Vice President of Innovent Biologics Group

"With the rapid development of ADC drugs in the field of oncology therapy, Innovent has been actively deploying in the field of ADC and continuing to develop and innovate. At this ESMO conference, we demonstrated for the first time the excellent safety and efficacy data of IBI354 in a variety of advanced solid tumors, which fully demonstrates Innovent Biologics' capabilities in ADC drug development, and we will continue to invest in the clinical development of innovative ADC molecules based on our proprietary ADC technology platform to provide patients with more and better treatments." "

concerning IBI354 (anti-HER2 antibody-camptothecin derivative conjugate)

IBI354 is an anti-HER2 monoclonal antibody-camptothecin derivative conjugate based on Innovent's innovative ADC linker-payload NT3 technology platform. IBI354 has a drug-to-antibody ratio (DAR) value of 8, which is able to carry more toxin load to tumor cells; ADC molecule has good hydrophilicity and excellent PK performance in vivo; The toxin small molecule has a strong ability to penetrate the cell membrane and exhibits a better bystander effect. The very low concentration of free toxin small molecules in plasma results in lower off-target toxicity and better safety. IBI354 has not only demonstrated good anti-tumor activity in a variety of tumor-bearing pharmacological models, but also demonstrated outstanding tumor inhibitory efficacy in HER2-targeted therapy resistance and metastasis models. Based on urgent clinical needs, Innovent is conducting clinical studies in China, United States and Australia to explore the efficacy and safety of IBI354 in various advanced malignancies. Based on this innovative ADC linker-payload NT3 platform, Innovent is advancing clinical trials of multiple self-developed ADC molecules, which have initially demonstrated excellent safety and efficacy signals.

About Innovent Biologics:

It is the mission and goal of Innovent Biologics to develop high-quality biologics that people can afford. Founded in 2011, Innovent is committed to developing, manufacturing and commercializing innovative medicines for major diseases such as oncology, autoimmunity, metabolism, and ophthalmology, so that our work can benefit more lives. The company has 11 products approved for marketing, they are sintilimab injection (Tyvyt ®), bevacizumab injection (Dayutong ®), adalimumab injection (Sullison ®), rituximab injection (Darbohua ®), pemetinib tablets (Darbertine ®), orebatinib tablets (Nericon ®), ramucirumab injection (Xiranze ®), selpercatinib capsules (Ruito ®), igneolleucel injection (Focosu ®), tolecimab injection (Symbile ®) and fluzerexib tablets (Dabert). ® At present, there are 3 varieties in the NMPA review, 4 new drug molecules have entered phase III or pivotal clinical studies, and 18 new drug varieties have entered clinical studies.

The company has reached more than 30 strategic partnerships with international partners such as Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center. While continuously developing innovative drugs and pursuing its own development, Innovent Biologics adheres to the people-centered development philosophy of economic construction. Over the years, we have always had scientific kindness in mind, adhered to the "patient-centered", cared about patients and their families, and actively fulfilled our social responsibilities. The company has successively initiated and participated in a number of pharmaceutical public welfare assistance projects, so that more and more patients can benefit from the progress of life sciences and buy and afford high-quality biological drugs. By the end of 2023, Innovent Patient Assistance Program had benefited more than 170,000 ordinary patients, with a total value of RMB 3.4 billion in drug donations. Innovent hopes to work with you to improve the development of China's biopharmaceutical industry to meet the people's access to medicines and people's pursuit of good wishes for life and health.

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