Editor's Note: The highly anticipated 2024 American Society of Clinical Oncology (ASCO) Annual Meeting has officially begun. As a premier global academic conference in oncology, ASCO attracts professionals from around the world to share and discuss the latest clinical oncology research findings and treatment advancements. At this year's conference, the research led by Professor Yu Chen from Fujian Cancer Hospital, titled "First-In-Class PD-1/IL-2 Bispecific Antibody Fusion Protein IBI363 for Advanced Melanoma," has been selected for poster presentation. This study marks the global debut of the independently developed IBI363 by Innovent Biologics for melanoma treatment, highlighting significant progress in evaluating its safety, tolerable dosage, and efficacy, especially in acral and mucosal melanoma subtypes specific to China.Study Overview
Study Title:
First-In-Class PD-1/IL-2 Bispecific Antibody Fusion Protein IBI363 for Advanced Melanoma: Phase I Study Results on Safety and Efficacy (Abstract No. 9562)
Background: Despite significant success with immunotherapy in advanced melanoma, there remains an unmet clinical need for patients resistant to immunotherapy and those with “cold” tumors. IBI363 is a first-in-class PD-1/IL-2α-biased bispecific antibody fusion protein designed to block the PD-1 checkpoint while delivering alpha-biased IL2 signals through cis-activation to rejuvenate exhausted tumor-specific T cells. Here, we report the latest results from a Phase I study evaluating the safety and efficacy of IBI363 in patients with advanced melanoma.
Methods: Patients with advanced melanoma who had failed standard treatments or were intolerant to them were enrolled and received different dose levels of IBI363 administered intravenously, ranging from 100 to 2000 μg/kg, on QW/Q2W/Q3W schedules. The primary endpoint was safety, and secondary endpoints included efficacy assessed by investigators per RECIST v1.1, comprising objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and progression-free survival (PFS).
Results: As of January 11, 2024, 67 patients were enrolled (55.2% female, median age 59.0 years, ECOG PS 1: 74.6%, previous treatment lines ≥2: 59.7%, prior immunotherapy: 89.6%). This included 17 cases of cutaneous melanoma, 22 cases of acral melanoma, 25 cases of mucosal melanoma, and 3 cases of unknown primary melanoma. The median treatment duration was 12.0 weeks (range: 2.0-43.6), with 38 patients (56.7%) still undergoing treatment. Disease progression was the most common reason for treatment discontinuation (25 patients, 37.3%). All patients were included in the safety analysis. 63 patients (94.0%) experienced treatment-emergent adverse events (TEAEs). There were 16 patients (23.9%) and 12 patients (17.9%) who experienced grade 3 or higher TEAEs and treatment-related adverse events (TRAEs), respectively. Common TEAEs (≥20%) included arthralgia (34.3%), hyperthyroidism (29.9%), and anemia (25.4%). One patient (1.5%) experienced a TEAE leading to treatment discontinuation. No patient deaths were attributed to TEAEs. Patients with at least one post-baseline tumor assessment were included in the efficacy analysis. Among evaluable patients (n=57), one achieved complete response (CR), 15 achieved partial response (PR), 25 had stable disease (SD), and 16 had progressive disease (PD). The overall ORR was 28.1% (95% CI: 17.0-41.5), and the DCR was 71.9% (95% CI: 58.5-83.0). Among patients with prior immunotherapy (n=52), the ORR was 21.2% (95% CI: 11.1-34.7) and the DCR was 67.3% (95% CI: 52.9-79.7). For those treated with 1 mg/kg Q2W (n=25), the ORR was 32.0% (95% CI: 14.9-53.5) and the DCR was 80.0% (95% CI: 59.3-93.2). Duration of response (DoR) and progression-free survival (PFS) data were not yet mature at the time of analysis. Baseline tumor region biomarker analysis showed significantly higher CD8+ T cell infiltration (measured by cell positivity and density) in PR/SD patients compared to PD patients (P<0.05).
Conclusion: IBI363 demonstrated encouraging efficacy across different melanoma subtypes and prior immunotherapy patients, with an acceptable and manageable safety profile in advanced melanoma patients. Further clinical development of IBI363 for melanoma is ongoing in China and internationally.
About the Melanoma Specialty Group
The melanoma specialty group at Fujian Cancer Hospital is the province’s first comprehensive treatment team specializing in melanoma. The group consists of experts from oncology, surgery, radiology, pathology, gynecology, ultrasound, and nursing, forming one of the nation’s top teams for melanoma comprehensive diagnosis and treatment. It serves as a model for standardized melanoma treatment, a hub for difficult case management, and a center for new drug and technology development. The primary ward, 19th Ward, has 33 open beds, admitting approximately 200 new melanoma patients and discharging nearly 3000 patients annually.
In recent years, the group has engaged in extensive learning and collaboration with major melanoma centers in China, including Peking University Cancer Hospital and Fudan University Shanghai Cancer Center, developing melanoma diagnosis and treatment strategies suitable for Fujian. After nearly a decade of development, Fujian Cancer Hospital has established a comprehensive melanoma diagnosis and management system, providing standardized treatment for melanoma patients in Fujian and surrounding regions, reducing the need for out-of-province treatment and economic burden.
