At the 2024 European Society for Medical Oncology (ESMO) Congress, Innovent presented the world's first Phase I clinical trial of the PD-1/IL-2α-bias bispecific antibody fusion protein IBI363 in combination with bevacizumab in patients with advanced colorectal cancer

SAN FRANCISCO, United States and SUZHOU, 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, announced the world's first-in-class PD-1/ at the 2024 European Society for Medical Oncology (ESMO) Congress. Phase I clinical data of IL-2α-bias bispecific antibody fusion protein IBI363 in combination with bevacizumab in the treatment of advanced colorectal cancer. Currently, Innovent is conducting Phase 1/2 clinical studies in China, United States and Australia to explore the efficacy and safety of IBI363 in various advanced malignancies.

PD-1/IL-2α-bias

Bispecific antibody fusion proteins ( IBI363) in combination with bevacizumab in patients with advanced colorectal cancer

The data from this study are from a Phase I clinical study to evaluate the safety, tolerability and preliminary efficacy of IBI363 in combination with bevacizumab in subjects with advanced colorectal cancer.

common Thirty-five subjects were treated with IBI363 in combination with Bevac, demonstrating breakthrough anti-tumor efficacy and a favorable safety profile

• As of August 30, 2024, a total of 35 subjects with advanced colorectal cancer have received different dose levels (0.6 mg/kg IBI363 plus 5 mg/kg Bevac Q2W, 1 mg/kg IBI363 plus 5 mg/kg Bevac Q2W, 1.5 mg/kg IBI363 plus 7.5 mg/kg Bevac Q3W). Among them, 91.4% of the subjects had advanced colorectal cancer with microsatellite stable (MSS) or mismatch repair protein intact (pMMR), and 8.6% of the subjects had unknown MSI/MMR status. 91.5% of the participants had received 2 or more prior lines of systemic antitumor therapy. Liver metastases were present in 51.4% of participants. 25.7% of participants had received immunotherapy prior to enrollment. Forty percent of subjects had mutations in the KRAS/NRAS exon 2/3/4 gene.
• In terms of safety, the most common treatment-related adverse events (TRAEs) were arthralgia, thyroid dysfunction, and rash. The overall incidence of grade 3 or above TRAEs was 22.9%, and the overall incidence of grade 3 or above immune-related adverse events (irAEs) was 5.7%. IBI363 in combination with bevacizumab had a similar safety profile compared with IBI363 alone, and no new safety risks were identified.

at In subjects with MSS/pMMR colorectal cancer, durable objective responses and long-term benefit trends were observed, demonstrating breakthrough therapeutic potential

• In terms of effectiveness, a total of 32 subjects underwent at least one post-baseline tumor assessment. The ORR was 21.9% (confirmed ORR was 15.6%) and the DCR was 65.6%. As of the data cut-off, the median DoR of all efficacy evaluable subjects was 8.1 months (95% CI: 1.5~8.2). The median PFS follow-up time was 7.6 months (95% CI: 4.0~9.4), the median PFS was 4.1 months (95% CI: 1.7~8.1), and the 6-month PFS rate was 47.7%. Median OS has not yet been reached.

Promising efficacy signals were observed in colorectal cancer subjects with liver metastases at baseline and colorectal cancer subjects without liver metastases at baseline

• Seventeen subjects with colorectal cancer with liver metastases at baseline underwent at least one post-baseline tumor evaluation, The ORR was 11.8% and the DCR was 58.8%.
• Fifteen subjects with colorectal cancer without liver metastases at baseline underwent at least one post-baseline tumor evaluation, The ORR was 33.3% and the DCR was 73.3%.

Encouraging signs of efficacy were observed in both colorectal cancer subjects who had received prior immunotherapy and colorectal cancer subjects who had not received prior immunotherapy

• Eight subjects with colorectal cancer who had received prior immunotherapy underwent at least one post-baseline tumor evaluation, The ORR was 25.0% and the DCR was 62.5%.
• Twenty-four subjects with colorectal cancer who had not received prior immunotherapy underwent at least one post-baseline tumor evaluation, The ORR was 20.8% and the DCR was 66.7% 。

in existence Promising efficacy signals were observed in colorectal cancer with KRAS/NRAS exon 2/3/4 mutations and in colorectal cancer subjects without RSA exon 2/3/4 mutations

• Fourteen subjects with colorectal cancer with RAS exon 2/3/4 mutations underwent at least one post-baseline tumor evaluation, The ORR was 21.4% and the DCR was 57.1%.
• Ten subjects with colorectal cancer without RAS exon 2/3/4 mutations underwent at least one post-baseline tumor evaluation, The ORR was 30.0% and the DCR was 90.0%.

Earlier, data from IBI363 monotherapy in the colorectal cancer cohort in another Phase I clinical study were previously presented at the 2024 ASCO Congress, demonstrating promising efficacy signals and good tolerability. At present, various studies on IBI363 are continuing to explore the prospects of IBI363 in tumors such as non-small cell lung cancer, melanoma, colorectal cancer, and IBI363 combination in MSS/pMMR advanced colorectal cancer, and relevant data and analysis will continue to be updated in future academic conferences or journals.

Professor Zhang Tao from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

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"Colorectal cancer is a common malignant tumor of the digestive system that seriously endangers human health. Worldwide, colorectal cancer ranks third in incidence and fourth in mortality among malignant tumors [1]. Although there has been some progress in the treatment of colorectal cancer in recent years, the toxicity of chemotherapy drugs and the resistance of some patients to traditional chemotherapy drugs are still serious problems in the treatment of colorectal cancer. Immunotherapy has brought new hope to patients with advanced colorectal cancer, but immunotherapy is only approved for patients with advanced colorectal cancer with MSI-H or dMMR. Several studies have shown that immunotherapy has very limited efficacy in patients with advanced colorectal cancer without MSI-H or dMMR [2]. IL-2, as an important cytokine that activates tumor-specific CD8+ T cells, is mechanistically complementary to immune checkpoint inhibitors and can reverse T cell exhaustion and thus overcome immune resistance. IBI363, a PD-1/IL-2α-bias bispecific molecule, in combination with bevacizumab, demonstrated breakthrough anti-tumor activity in patients with advanced colorectal cancer without MSI-H or dMMR, showing clinical benefit in both ORR and PFS with a manageable safety profile. It also showed good anti-tumor activity in colorectal cancer patients with or without liver metastases, prior immunotherapy, or with or without KRAS/NRAS exon 2/3/4 mutations. IBI363 in combination with bevacizumab observed encouraging objective response rates and disease control rates, as well as durable objective response and long-term benefit trends in colorectal cancer with little response to immunotherapy, with no new safety risks. Overall, the existing clinical data suggest that IBI363 combined with Bevac has sufficient development prospects in colorectal cancer population, and its clinical value is worth further exploring. "

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

"Based on ASCO's data reports, we presented data from IBI363 combination therapy at this ESMO Annual Meeting. In non-MSI-H/dMMR advanced colorectal cancer, the low- and medium-dose IBI363 in combination with bevacizumab demonstrated powerful anti-tumor effects, observed a trend of durable objective response and long-term benefit, and led to breakthrough results. Seeing such results in a population with relatively cold tumors augurs well for the broad development potential of IBI363, and we look forward to the data at higher doses and longer follow-up of IBI363 to lay a solid foundation for advancing the next step of clinical development." "

concerning

IBI363(PD-1/IL-2α-bias双特异性抗体融合蛋白)

IBI363 is a world-first PD-1/IL-2 bispecific fusion protein independently developed by Innovent Biologics, which has both the functions of blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 has been designed to retain its affinity for IL-2 Rα but weaken the binding ability of IL-2Rβ and IL-2Rγ to reduce toxicity. The PD-1 binding arm can achieve both PD-1 blocking and selective delivery of IL-2. Since newly activated tumor-specific T cells express both PD-1 and IL-2α, this differential strategy can be more precise and efficient in targeting and activating this T cell subset. IBI363 not only showed good anti-tumor activity in a variety of tumor-bearing pharmacological models, but also showed outstanding tumor inhibitory efficacy in PD-1 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 IBI363 in various advanced malignancies.

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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Disclaimer: Innovent does not recommend any unapproved drugs/indications.

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2、 Baraibar I, Mirallas O, Saoudi N et al. Combined Treatment with Immunotherapy-Based Strategies for MSS Metastatic Colorectal Cancer. Cancers (Basel). 2021 Dec 16; 13(24):6311.