Innovent Biologics announced that the first patient has been dosed in a pivotal study evaluating IBI363 (Takeda R&D code: TAK-928), a potential first-in-class PD-1/IL-2α-biased bispecific fusion protein, in combination with bevacizumab versus investigator's choice of therapy, in patients with advanced colorectal cancer (CRC) that is refractory or intolerant to standard treatment.

This is the third pivotal registrational clinical study initiated for IBI363 and marks a critical step forward for investigational next-generation Immuno-Oncology (IO) therapies in overcoming colorectal cancer—a classic 'immune-cold' tumor.

Previously initiated studies of IBI363 include a pivotal phase 2 clinical study (NCT07217301) in China for IO-naïve melanoma (acral and mucosal subtypes). A global, multi-center, phase 3 clinical study (NCT06797297) in IO-resistant squamous Non-Small Cell Lung Cancer (NSCLC) has also been initiated. As part of a license and collaboration agreement, Innovent and Takeda are co-developing IBI363/TAK-928 globally and will co-commercialise IBI363/TAK-928 in the US Takeda will exclusively commercialise IBI363/TAK-928 worldwide outside of the US and greater China.

This trial (NCT07722494) is a multicenter, randomised, open-label, phase 3 clinical study designed to evaluate the efficacy and safety of IBI363 in combination with bevacizumab compared with investigator's choice of therapy in patients with advanced colorectal cancer who have failed or are intolerant to standard therapies. A total of 550 patients are planned to be enrolled. The primary endpoint of this study is Overall Survival (OS). This study is being conducted in China where Innovent holds development and commercialisation rights for IBI363/TAK-928.

At the 2025 ASCO Annual Meeting, data from a phase 1 clinical study of IBI363 for the treatment of advanced colorectal cancer was presented as an oral presentation. IBI363 in combination with bevacizumab demonstrated encouraging efficacy signals and a manageable safety profile.

Among patients treated with IBI363 in combination with bevacizumab (n=73), the overall confirmed Objective Response Rate (cORR) was 15.1 percent, and the Disease Control Rate (DCR) was 61.6 percent. With a median follow-up of 9.9 months, the Progression-Free Survival (PFS) reached 4.7 months. With a median follow-up of 9.4 months, Overall Survival (OS) data remained immature, with only 13 events (17.8 percent) observed.

The overall safety profile was clinically manageable, and no new safety signals were observed. The incidence of grade 3 or higher Treatment-Related Adverse Events (TRAEs) in the combination therapy group was 35.6 percent. The most common TRAEs were arthralgia, anemia, rash, and hypothyroidism.

Professor Kefeng Ding from the Second Affiliated Hospital of Zhejiang University School of Medicine, the principal investigator of this study, stated, "Colorectal cancer is a common gastrointestinal malignancy that poses a severe threat to human health. Worldwide, it ranks 3^rd in incidence and 2^nd in mortality among all malignant tumors. Approximately, 86 percent of colorectal cancers are in an immune-desert or immune-suppressed state, rendering them unresponsive to traditional Immune Checkpoint Inhibitors (ICIs). For patients with colorectal cancer who have failed standard therapy, treatment options are limited, survival is short, and there remains a huge unmet clinical need. As a PD-1/IL-2α-biased bispecific molecule, IBI363's dual antitumor mechanism—blocking PD-1 while stimulating tumor-specific CD8? T cells (TST cells)—holds the promise of turning 'cold' tumors 'hot'. Early data for IBI363 in combination with bevacizumab in late-line treatment have demonstrated encouraging, breakthrough efficacy along with tolerable safety, showing potential to become a novel immunotherapy for colorectal cancer. I will work closely with other investigators to advance and complete this pivotal clinical study, steadily generating high-quality clinical data to provide colorectal cancer patients with a more effective treatment option."

Based on updated long-term follow-up data from the above study, IBI363 in combination with bevacizumab was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) in May 2026. The proposed indication is for patients with advanced microsatellite stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer (CRC) who have progressed on ≥ 2 lines of prior standard therapy. The updated study results are planned for presentation at a future international academic conference or publication in an international academic journal.

Dr. Hui Zhou, Chief R&D Officer (Oncology), Innovent, stated, "IBI363 represents the evolutionary direction of next-generation immunotherapy—not only potentially improving on the survival benefits of existing IO therapies, but also striving to overcome 'cold' tumors that traditional IO treatments cannot effectively address. Early clinical data demonstrate that IBI363 in combination with bevacizumab achieves significant responses and long-term survival benefits in non-MSI-H/pMMR advanced colorectal cancer, validating its unique mechanism and broad-spectrum potential. Currently, the first batch of core indications for IBI363 has smoothly entered pivotal registration clinical trials. We look forward to offering a new choice for colorectal cancer patients and bringing hope to broader unaddressed areas in immunotherapy."