Keynote-G08: An open-label, multicenter, dose escalation and expansion phase I/II study of GI-102 (CD80/IL2v3) in advanced solid tumors (part A and D of GII-102-P101)

초록

Background GI-102 (CD80/IL2v3) is a novel immunocytokine designed to direct interleukin-2 variant (IL-2v3) to immune and tumor cells. Initial monotherapy results from Part A were presented at ASCO 2024. Here, we report final Part A results and preliminary Part D data evaluating GI-102 with pembrolizumab. Methods KEYNOTE-G08 is a phase 1/2 study evaluating safety, tolerability, and anti-tumor activity of GI-102 in patients (pts) with metastatic solid tumors who failed standard care. In Part A, GI-102 (0.06–0.45 mg/kg) was administered IV every 3 weeks (Q3W). In Part D, pts received GI-102 (0.24 or 0.35 mg/kg) with pembrolizumab (200 mg) Q3W. Results As of 24 Apr 2025, 54 pts received GI-102 in Part A. Median age was 62 years; 72.2% had prior immunotherapy (IO); median prior therapies: 3. No dose-limiting toxicities were observed up to 0.45 mg/kg. Common treatment-related adverse events (≥30%) were pyrexia [72.2%] and chills [44.4%]. Among 41 efficacy-evaluable pts (0.06–0.35 mg/kg), the objective response rate (ORR) was 17.1% and disease control rate (DCR) 53.7%, with responses in melanoma, non-small cell lung cancer, renal pelvis cancer, ovarian cancer, and Merkel cell carcinoma. Notably, Immune profiling and tumor microenvironment analysis showed ORR correlated with higher CD8+ T/Treg and NK/Treg ratios. The single-dose recommended phase 2 dose (sRP2D) was defined as 0.35 mg/kg. At sRP2D, ORR was 18.2%, DCR 63.6%, and median progression-free survival (mPFS) 5.3 months (0.8–8.4+). In Part D, 11 pts refractory or resistant to prior IO have been enrolled. The combination was well tolerated. Among 3 evaluable pts at 0.24 mg/kg GI-102 + pembrolizumab, 2 had PR, 1 had PD, ORR 66.7%, median duration of treatment (mDOT) 3.3+ months. Significant CD8+ T cell expansion was noted with minimal impact on Treg. Conclusions GI-102 has shown promising monotherapy activity in patients who have failed standard care, with ORR closely correlated with the effector/Treg cell ratio. Early data from combination with pembrolizumab suggest encouraging activity in IO-refractory or resistant tumors. The study is ongoing with continued enrollment.