Head-to-Head Against Pembrolizumab: Innovent Announces First Patient Dosed in the First Pivotal Study of IBI363 in Melanoma

Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology, and other major diseases, announced that the first patient has been dosed in its registrational study evaluating IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, as monotherapy versus pembrolizumab (Keytruda®) in patients with unresectable locally advanced or metastatic mucosal or acral melanoma who have not received prior systemic therapy. This is IBI363's first pivotal study and a significant milestone for China's innovative immuno-oncology (IO) therapy in addressing the global challenge of treating "cold tumors."

This is a randomized, multicenter, pivotal study designed to evaluate the efficacy and safety of IBI363 monotherapy versus pembrolizumab monotherapy in patients with unresectable, locally advanced or metastatic mucosal or acral melanoma who have not received prior systemic therapy. The primary endpoint is progression-free survival (PFS), as assessed by an Independent Radiology Review Committee (IRRC) based on RECIST v1.1 criteria.

IBI363 has demonstrated outstanding efficacy signals in immunotherapy (IO)-naïve melanoma patients across two earlier clinical trials (Phase 1a/1b study NCT05460767 and Phase 2 study NCT06081920), which enrolled a total of 26 patients with advanced acral or mucosal melanoma:

●The overall objective response rate (ORR) was 61.5%, and the disease control rate (DCR) was 84.6%—significantly higher than current domestic immunotherapy standards.

●Prolonged follow-up revealed sustained tumor responses and long-term benefits, suggesting the potential superiority of IBI363 over existing standard therapies.

These preliminary data were presented at SITC 2024[1], and updated follow-up results will be shared at international conferences in 2025.

IBI363 has also demonstrated a manageable safety profile. To date, IBI363 monotherapy or combination therapy has been administered to hundreds of patients with advanced solid tumors globally. The overall safety profile remains consistent with known toxicities of PD-1/PD-L1 and IL-2 therapies, with common treatment-related adverse events (TRAEs) including arthralgia, anemia, thyroid dysfunction, and rash—all of which are manageable with routine clinical care.

Professor Jun Guo, Principal Investigator of the Study and Director of Peking University Cancer Hospital, stated: "Melanoma has a high mortality rate in China, and its incidence is rising annually. IO-naïve melanoma patients currently have a median PFS of only around three months, reflecting a significant unmet clinical need. Moreover, non-cutaneous subtypes like mucosal melanoma—which are more prevalent in China—are particularly resistant to immunotherapy with limited clinical benefits. IBI363 has shown the potential to convert 'cold tumors' into 'hot tumors' by the dual activation of PD-1 and IL-2 pathways. Encouraging efficacy observed in Phase 1a/1b and 2 studies suggest its potential as a next-generation IO therapy for melanoma. Along with my fellow investigators, I hope this trial will lead to more effective treatment options for patients with acral and mucosal melanoma."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "As Innovent's first-in-class next-generation IO therapy, IBI363 simultaneously and selectively inhibits the PD-1/PD-L1 pathway and activates the IL-2 pathway. In previous studies, IBI363 has demonstrated outstanding efficacy and safety in melanoma and multiple cancer types. This pivotal trial, through a head-to-head comparison with pembrolizumab, aims to validate IBI363's potential as a superior treatment option for melanoma patients over the current standard-of-care. We are also accelerating the global development of IBI363 across multiple tumor types, with the goal of extending the benefits of China's innovation to patients worldwide."

About IBI363 (First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein))

IBI363 is a first-in-class drug candidate independently developed by Innovent Biologics. It is a PD-1/IL-2 bispecific antibody fusion protein designed to enhance efficiency while minimizing toxicity. The IL-2 arm of IBI363 has been engineered to optimize therapeutic effects with reduced side effects, while the PD-1 binding arm enables PD-1 blockade and selective IL-2 delivery. By simultaneously inhibiting the PD-1/PD-L1 pathway and activating the IL-2 pathway, IBI363 facilitates more precise and efficient targeting and activation of tumor specific T cells. Preclinical studies have shown that IBI363 exhibits strong anti-tumor activity across multiple tumor-bearing pharmacological models, including those resistant to PD-1 inhibitors and metastatic models. Additionally, it has demonstrated a favorable safety profile in preclinical models.

Clinical trials of IBI363 are currently underway in China, the United States, and Australia to evaluate its safety, tolerability and preliminary efficacy in subjects with advanced malignancies. The first pivotal study of IBI363 has been initiated, for the treatment of IO-naive mucosal or acral melanoma. Furthermore, IBI363 has received two fast track designations (FTD) from the U.S. FDA, for the treatment of squamous non-small cell lung cancer and melanoma, respectively.

About Melanoma

Melanoma is a malignant tumor that develops from melanocytes. Although melanoma accounts for only 3% of all types of skin cancer, it has the highest motality rate of all types and is the most likely to metastasize. In China, the incidence and mortality rate of melanoma continue to rise. Melanoma is classified into three main subtypes:  cutaneous, acral and mucosal. The characteristics of melanoma in Chinese patients differs greatly from those seen in European and American Caucasian populations in terms of pathogenesis, biological behavior, histological morphology, treatment response and prognosis[4]. For advanced cutaneous and acral melanomas, patients with the BRAF V600 mutation typically receive BRAF inhibitor combined with MEK inhibitors as the preferred molecular targeted therapy. For those without the BRAF V600 mutation, chemotherapy combined with anti-angiogenic drugs can be is a first-line treatment option. Notably, immunotherapy has not yet been approved as the first-line treatment indication for advanced melanoma in China. For second-line treatment, therapies not previously used in first-line settings are recommended. Patients who have not received PD-1 monoclonal antibody in the first-line setting may be treated with PD-1 inhibitors as a second-line option. For advanced mucosal melanoma, chemotherapy or PD-1 monoclonal antibody combined with anti-angiogenic drugs can be considered first-line treatment. For those with BRAF V600 mutation, BRAF inhibitor ±MEK inhibitor can be selected. Currently, posterior treatment options for melanoma are very limited.

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 14 products in the market. It has 4 new drug applications under regulatory review, 2 assets in Phase III or pivotal clinical trials and 17 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.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.