IBI363 Receives FDA Fast Track Designation for Advanced/Metastatic Melanoma

FDA

The FDA has granted fast track designation to the PD-1/IL2α bispecific antibody fusion protein IBI363 as monotherapy for the treatment of patients with unresectable locally advanced or metastatic melanoma, excluding choroidal melanoma, that has progressed after 1 or more prior lines of systemic therapy, including a PD-1/PD-L1 inhibitor.¹

Findings from a phase 1a/1b trial (NCT04085185), which were presented at the June 2024 ESMO Virtual Plenary meeting demonstrated that among evaluable patients with melanoma who had previously been treated with immunotherapy who received 1 mg/kg of IBI363 in the study and underwent 1 or more tumor evaluations after baseline (n = 37), 11 achieved objective responses, including 1 complete response (CR) and 10 partial responses (PRs), translating to an overall response rate (ORR) of 29.7%. The disease control rate (DCR) in this population was 73.0%. Among 8 immuno-oncology (IO)–naive patients with mucosal melanoma, the ORR was 75.0%, including 1 CR and 5 PRs. The DCR in this population was 100%.

“Melanoma is the most common fatal skin cancer in Europe and the United States [US]. In China, while melanoma is a rare malignant tumor, it has a high fatality rate, and its incidence is steadily increasing each year. Despite the success of immune checkpoint inhibitors in the treatment of melanoma, there is currently no drug approved for immunotherapy-failed melanoma around the world, and the ORR [with] traditional chemotherapy [with or without] anti-vascular therapy for immunotherapy-failed melanoma is only 3.8% to 6.8%, with a median progression-free survival of less than 3 months, and the benefit is very limited,” Hui Zhou, PhD, senior vice president of Innovent Biologics, stated in a news release.

Phase 1/2 trials are ongoing in the US, China, and Australia to evaluate the efficacy and safety of IBI363 in patients with a variety of malignant tumors.

In the phase 1 trial, at a data cutoff date of April 16, 2024, 347 patients with advanced solid tumors received IBI363 monotherapy at a range of 0.2 μg/kg weekly to approximately 3 mg/kg once every 3 weeks.² Patients had non–small cell lung cancer (n = 100), melanoma (n = 89), colorectal cancer (CRC; n = 102), and other cancers (n = 56). A total of 81.8% of patients had received at least 2 prior lines of systemic therapy. In total, 84.1% of patients with solid tumors other than CRC (n = 245) had received prior immunotherapy.

Three hundred patients received IBI363 at a dose of at least 0.1 mg/kg and underwent at least 1 post-baseline tumor assessment. In total, 3 patients had a CR, and 49 patients had a PR. As of the data cutoff, 38 responders were still free of disease progression, and the duration of response data were immature. Among the 204 patients who had received prior IO-based therapy, the ORR was 17.6%.

Treatment-related adverse effects (TRAEs) of grade 3 or higher occurred in 23.9% of patients. The most common TRAEs were arthralgia, anemia, hypothyroidism, and hyperthyroidism. Immune-related AEs of grade 3 or higher were observed in 10.4% of patients. Among the patients who received IBI363 at 3 mg/kg every 3 weeks (n = 38), 13.2% had TRAEs of grade 3 or higher. However, in this population, the safety profile of the agent was similar to that observed in the overall population, and investigators identified no new safety signals.

“There is an urgent clinical need for patients who have previously [progressed on] immunotherapy,” Zhou added in a news release.¹ “As a first-in-class PD-1/IL-2α–bias bispecific antibody fusion protein, IBI363 monotherapy has shown encouraging efficacy and a favorable safety profile in [patients with] melanoma who have previously received immunotherapy. We will continue to explore the efficacy and safety of IBI363 in melanoma to provide more effective clinical treatment for patients with immune-resistant melanoma."

References

1. Innovent receives fast track designation from the U.S. FDA for IBI363 (PD-1/IL-2α bispecific antibody fusion protein) as monotherapy for advanced melanoma. News release. Innovent Biologics. September 4, 2024. Accessed September 4, 2024. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=480
2. Innovent delivers oral presentation on clinical data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) in advanced non-small cell lung cancer and other solid tumors at the 2024 ESMO Virtual Plenary. News Release. Innovent Biologics. June 14, 2024. Accessed September 4, 2024. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=459