On June 1, 2025 Innovent Biologics, Inc (Suzhou) (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, reported the data from Phase 1 and Phase 2 clinical studies of IBI363, first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, for the treatment of "immune cold tumor" —immunotherapy-pretreated melanoma (acral and mucosal subtypes) were orally presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. IBI363 has shown breakthrough efficacy in patients with heavily-treated melanoma subtypes – which are traditionally treatment-resistant "cold" tumors, and a pivotal registration trial for IBI363 is currently ongoing (Press release, Innovent Biologics, JUN 1, 2025, View Source;bias-bispecific-antibody-fusion-protein-from-phase-1-and-2-clinical-studies-on-immunotherapy-treated-advanced-malignant–302470081.html [SID1234653565]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Innovent Biologics is conducting clinical studies in China, the United States, and Australia to explore the efficacy and safety of IBI363 for multiple tumor indications, including immune resistance, cold tumors, and front-line treatments. At this year’s ASCO (Free ASCO Whitepaper) meeting, IBI363 reported encouraging Phase 1/2 clinical data in the first three indications explored—non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and melanoma—focusing on IO-resistant and cold tumors. The data comprehensively demonstrated the breakthrough clinical outcomes of IBI363 across these indications, from robust tumor response to long-term survival benefits. These findings provide strong support of the drug’s novel mechanism of action translating effectively into clinical outcomes, and imply its potential for broader clinical development, offering new hope in areas of immunotherapy where treatment options remain limited.
A Phase 1/2 clinical study of PD-1/IL-2α-bias bispecific antibody fusion protein (IBI363) in the treatment of advanced "cold" tumor subtypes (acral and mucosal) malignant melanoma
The data presented at this ASCO (Free ASCO Whitepaper) meeting are from two multi-center Phase 1 and 2 clinical studies (registration no.: NCT05460767, NCT06081920) designed to evaluate the efficacy and safety of IBI363 monotherapy in the treatment of advanced melanoma. As of April 7, 2025, a total of 31 patients with unresectable, locally advanced or metastatic acral and mucosal melanoma who had previously received immunotherapy were enrolled and treated at the dosage of 1 mg/kg Q2W, and 64.5% of them had ≥2 lines of prior treatment.
Breakthrough efficacy of IBI363 monotherapy has been achieved in patients with "immune-cold" melanoma, with notable durable response and prolonged survival benefit:
In patients with at least one post-baseline tumor assessment (n=30), the confirmed objective response rate (cORR) was 23.3%, including 25.0% for mucosal type and 20.0% for acral type. The disease control rate (DCR) reached 76.7%, with 85.0% in mucosal type and 60.0% in acral type.
In patients treated with 1 mg/kg Q2W with confirmed responses (n=7), a durable response was observed with a median duration of response (DoR) of 14.0 months and events of 42.9%.
In patients treated with 1 mg/kg Q2W (n = 31) had a median progression-free survival (PFS) of 5.7 (2.7, 6.8) months, which was significantly longer than data from previous studies (PFS less than 3 months[1] ). The median follow-up time was 14.7 months, the median overall survival (OS) was 14.8 (9.9, NC) months, and the median OS of patients with mucosal subtype was 19.3 (9.9, NC) months. The overall 12-month OS rate was 61.5%.
In terms of safety, IBI363 was generally well tolerated. Among the subjects treated with 1 mg/kg Q2W (n = 31), the treatment-related adverse events (TRAEs) with an incidence > 30% were arthralgia, rash, and hyperthyroidism, most of which were Grade 1 or 2. The overall incidence of Grade ≥ 3 TRAEs was 29.0%, and only 3.2% of subjects discontinued treatment due to TRAEs. Overall safety was manageable, and no new safety risks were found.
Acral+Mucosal
(1mg/kg Q2W)
N=31
Confirmed ORR, % (95% CI)
23.3 (9.9, 42.3)
DCR, % (95% CI)
76.7 (57.7, 90.1)
Median PFS, months (95% CI)
5.7 (2.7, 6.8)
Median OS, months (95% CI)
14.8 (9.9, NC)
12-month OS rate, % (95% CI)
61.5 (39.8, 77.3)
Median OS follow-up, months
14.7
A pivotal Phase 2 registrational study of IBI363 in the treatment of advanced acral and mucosal malignant melanoma has been initiated
Innovent Biologics announced a trial in progress (TiP) . It is a randomized, open-label, multi-center Phase 2 study evaluating the efficacy and safety of IBI363 monotherapy compared to pembrolizumab (Keytruda) in patients with unresectable, locally advanced or metastatic mucosal and acral melanoma who have not received prior systemic treatment. As the first pivotal registration trial of IBI363, this study is designed to directly compare IBI363 monotherapy with pembrolizumab in this patient population. A total of 180 patients are planned to be enrolled and randomized in a 1:1 ratio. The primary endpoint is progression-free survival (PFS) assessed by an Independent Review Committee (IRC).
The first patient was dosed in March 2025, marking a significant step in advancing IBI363’s development in melanoma. Additional studies exploring IBI363 in combination therapies across other cancer types are also ongoing.
Professor Guo Jun from Peking University Cancer Hospital and the Principal Investigator of Melanoma Studies on IBI363 said: "Although melanoma is a relatively rare malignant tumor in China, it has a high mortality rate, and its incidence continues to rise each year. Historically, patients with melanoma who have not received immunotherapy have had a median PFS of only about 3 months, which highlights a significant unmet clinical need. Notably, non-cutaneous melanoma (especially mucosal melanoma) accounts for a large proportion of cases in China and is considered a ‘cold tumor’, typically unresponsive to traditional immunotherapy. In these cases, the response rate to PD-1 monotherapy is often below 15%, offering limited clinical benefit. More effective treatments are urgently needed[2]. IBI363 addresses this challenge by transforming ‘cold tumors’ into ‘hot tumors’ through dual activation of the PD-1 and IL-2 pathways. The data presented in this study showed that IBI363 delivers significantly improved efficacy compared to previous studies in cold tumor subtypes and standard of care therapies, while maintaining a favorable safety profile. IBI363 has the potential to become a new standard in immunotherapy for malignant melanoma in China, providing a long-needed treatment option for patients with acral and mucosal malignant melanoma."
Dr. Zhou Hui, Senior Vice President of Innovent Biologics, said: "At present, there is a huge unmet clinical need for the treatment of unresectable, locally advanced or metastatic mucosal and acral melanoma in China. Approved PD-1 therapies have not substantially improved first-line outcomes in melanoma, and the clinical benefits remain limited[3]. IBI363 is leading the evolution of next-generation immunotherapy. By leveraging a dual-mechanism of ‘PD-1 blockade + IL-2 directed activation’, IBI363 enhances T cell function and expands T cell populations to reshape the tumor immune microenvironment. IBI363 has shown excellent efficacy and safety results in the treatment of patients with immune-cold melanoma subtypes. A Phase 2 pivotal registrational study is currently underway. Positive results in patients with mucosal and acral melanoma are highly anticipated, offering hope for a more effective treatment option. Meanwhile, we are accelerating the global development of IBI363 across multiple tumor types, with the goal of making this innovative treatment accessible to patients around the world."
About Melanoma
Melanoma is a malignant tumor that develops from melanocytes. While it accounts for only 3% of all skin cancers, it has the highest mortality rate and is the most prone to metastasis. In China, both the incidence and mortality rates of melanoma are rising annually. Based on tumor location, melanoma is classified into cutaneous, acral, and mucosal subtypes. Melanoma in Chinese populations differs significantly from that in Caucasian populations in Europe and the United States with regard to pathogenesis, biological behavior, histological morphology, treatment methods, and prognosis[4]. For patients with advanced cutaneous and acral melanoma with BRAF V600 mutation, a combination of BRAF and MEK inhibitors is the preferred treatment. For those without this mutation, chemotherapy combined with anti-angiogenic drugs is often considered as first-line treatment. Although pembrolizumab was approved in Sep. 2024 for first-line treatment of melanoma, the clinical benefit of PD-1 inhibitors in this setting remains modest. In second-line treatment, agents different from those used in the first line are generally preferred. For patients not previously treated with a PD-1 inhibitor, it can be considered as a second-line option. In advanced mucosal melanoma, median PFS for patients without prior immunotherapy is only about 3 months. Given the limited efficacy of current treatments for non-cutaneous melanomas, especially mucosal subtypes, which are more prevalent in China, there is an urgent need for more effective therapies.
About IBI363 (PD-1/IL-2 α-bias bispecific antibody fusion protein)
IBI363 is the world’s first PD-1/IL-2α-bias bispecific fusion protein independently developed by Innovent Biologics. It integrates two key functions: blockade of the PD-1/PD-L1 pathway and activation of the IL-2 signaling pathway. The IL-2 arm of IBI363 has been engineered to retain affinity for IL-2 Rα while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. The PD-1 binding arm enables simultaneous PD-1 blockage and selective delivery of IL-2. This differential targeting strategy exploits the fact that newly activated tumor-specific T cells co-express PD-1 and IL-2α, which allows for more precise and efficient targeting and activation of this T cell subset. IBI363 not only showed good anti-tumor activity in a variety of tumor-bearing pharmacological models but also showed prominent anti-tumor efficacy in PD-1 resistance and metastasis models.
Driven by urgent clinical needs, Innovent Biologics is conducting clinical studies in China, the United States, and Australia to assess the efficacy and safety of IBI363 across multiple tumor types. The first pivotal registration trial of IBI363 has been initiated for the treatment of mucosal and acral melanoma without immunotherapy.
IBI363 has been granted two fast track designations by the FDA for the treatment of advanced squamous non-small cell lung cancer and melanoma, respectively. IBI363 has also been granted Two Breakthrough Therapy Designations by the National Medical Products Administration (NMPA) for the treatment of advanced melanoma and squamous NSCLC.