A first-in-human, phase 1/2a study of GI-102 (CD80-IL2v3) in patients with advanced or metastatic solid tumors: Initial results from dose escalation.
Authors: Jeeyun Lee, Byoung Chul Cho, Jae-Lyun Lee, Jung-Yun Lee, Wen Wee Ma, Alex A Adjei, Jian Li Campian, Yujie Zhao, Mahesh Seetharam, Byoung Yong Shim, Nari Yun, Woohyung Wayne Lee, Sujeong Park, Woosun Lee, Sosun Park, Jay Kim, Bochan Seo, Ryunhee Kim, Myoung Ho Jang
Journal: Journal of Clinical Oncology (2024)

2598 Background: GI-102 (CD80-IL2v3) is a novel immunocytokine designed to direct IL-2v3 to immune cells and tumor cells. IL-2v3 of GI-102 abolished affinity to IL-2Rα minimizing the impact of IL-2 on Treg cells. Preferential targeting of immune cells and further inhibition of CTLA-4 and PD-L1 via CD80 synergize with potent activity of IL-2v3, resulting in robust proliferation and activation of CD8+ T and NK cells. Here we report preliminary safety and efficacy data of GI-102 from a phase 1/2a trial in patients with metastatic solid tumors. Methods: NCT05824975 is an ongoing, dose escalation (3+3 design) and expansion study to evaluate safety, tolerability, PK, PD and anti-tumor activity of GI-102. Each dose level allows to enroll additional 7 patients to fully inform the safety, PK and PD at that dose level. GI-102 was administered intravenously every 3 weeks until disease progression or unacceptable toxicities. Disease was assessed every 6 weeks using RECIST v1.1. Results: As of 12 Jan 2024, 32 patients were treated in dose escalation: 8 at dose level 0.06 mg/kg, 10 at 0.12 mg/kg, 9 at 0.24 mg/kg and 5 at 0.45 mg/kg. Patients had received median of 3 [1-7] prior lines of therapy, including 25.0% (8/32) who had received ≥ 5 lines and 68.8% (22/32) had experienced immune checkpoint blockade (ICB). No dose-limiting toxicities (DLTs) were observed until the highest dose of 0.45 mg/kg Q3W. The most common treatment-related adverse events (TRAEs, ≥ 10%) were pyrexia [43.8%] and chills [34.4%]. 5 patients [15.6%] had ≥ Grade 3 TRAEs and no patient reported TRAEs leading to discontinuation of GI-102. In 23 patients (7 cutaneous melanoma, 4 non-small cell lung cancer, 3 ovarian cancer and others) who had at least 1 post-treatment tumor assessment, objective responses were observed in 17.4% (4/23). In patients with metastatic melanoma who previously experienced ICB, overall response rate (ORR) and disease control rate (DCR) was 42.9% (3/7) and 85.7% (6/7), respectively, including 3 confirmed partial responses (cPR). The median time to response (TTR) was 6 weeks and duration of response (DoR) was 6.0+, 2.4+ and 1.7+ month, respectively. In patients with metastatic ovarian cancer, ORR and DCR were 33.3% (1/3) and 66.7% (2/3), respectively, including 1 cPR [TTR of 6 weeks; DoR 1.9+ month]. Preliminary PK profile showed target-mediated drug disposition with a half-life of ~48 hours. 0.24 mg/kg of GI-102 resulted in a significant expansion of peripheral lymphocytes, CD8+ T cells (effector &amp; memory) and NK cells, by 4.4 [2.1-9.6], 3.9 [2.0–5.7] and 20.4 [9.5–32.6]-fold change from baseline, respectively. There was no meaningful increase in Treg cells. Conclusions: GI-102 was well tolerated up to dose of 0.45 mg/kg Q3W with meaningful monotherapy activity, regardless of previous ICB experience, in patients who failed on standard of care. The dose-escalation is currently ongoing to identify RP2D. Clinical trial information: NCT05824975 .