Background GI-101 (CD80-IL2v) is a novel immunocytokine, designed to direct IL-2v to tumor and immune cells. IL-2v of GI-101 is engineered to maximize the expansion of cytotoxic T and NK cells but not Treg cells, and CD80 further inhibits Treg cell function. GI-101 demonstrated single agent activity in an anti-PD-L1 experienced patient (ORR 5.9% in heavily-treated population).1 Here we report clinical outcomes from dose escalation of Part B of the study.
Methods Keynote-B59 is an ongoing, phase 1/2 study of GI-101 monotherapy and in combination with various agents in patients (pts) with advanced solid tumors. In dose escalation of Part B, pts received intravenous GI-101 (0.002~0.15 mg/kg) and pembrolizumab (200 mg) on day 1 of each 21-day cycle. The primary objective is to assess safety, tolerability and maximum tolerated dose (MTD) and/or combination RP2D (cRP2D).
Results As of 20 Apr 2023, 25 pts with any solid tumors who failed on standard of care received GI-101 plus pembrolizumab. The median number of prior therapies were 3 [1–9], and 64% were previously treated with immune checkpoint blockade (ICI) therapy. Treatment-related adverse events occurred in 23 pts (92%), with the most common events (≥ 20%) being pyrexia (48%), AST/AST increased (28%, 24%). One case of dose-limiting toxicity was observed; MTD was not reached. 0.15 mg/kg GI-101 Q3W was established as the cRP2D based on the desirable expansion of peripheral immune cells and anti-cancer activities. Objective responses were observed in 4 of 24 evaluable pts (ORR 16.7%) regardless of prior anti-PD(L)1 therapy; 2 confirmed PR in pts with NSCLC and clear cell RCC (ccRCC), both failed on previous anti-PD(L)1 therapy, and 2 unconfirmed PR in pts with metastatic carcinoma of unknown origin (MUO) and ccRCC. The ORR in pts who failed on previous ICI therapy was 13.3% while that of ICI-naïve population was 22.2%. Overall disease control rate was 66.7% including 4 pts of SD > 6 months. Pts who had objective response showed significantly higher level of central memory T and CD8+ T cell expansion in peripheral blood. In a patient achieved PR, significant infiltration of CD8+ T and NK cells were observed in tumor microenvironment with minimal impact on Treg cells.
Conclusions GI-101 was well tolerated when combined with pembrolizumab in pts with advanced solid tumors. GI-101 plus pembrolizumab demonstrated anti-tumor activity in a heavily pre-treated patient population, with prior anti-PD(L)1 therapies. The dose expansion phase of the study is currently ongoing.
Trial Registration Clinical trial identification: NCT04977453
Cho BC, Shin S, Lee JL, et al. Preliminary results of GII-101-P101 (Keynote-B59): GI-101 (CD80-IgG4 Fc-IL2v) as a single agent and in combination with pembrolizumab in patients with advanced and/or metastatic solid tumors. Journal for ImmunoTherapy of Cancer 2022;10:doi: 10.1136/jitc-2022-SITC2022.0718
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