An open-label, multicenter, phase I/II study of GI-101, CD80-IgG4 Fc-IL2v, in advanced solid tumors (Part A of GII-101-P101; KEYNOTE-B59)

초록

Background GI-101 is a novel immunocytokine containing CD80 and IL-2v. GI-101 monotherapy and with pembrolizumab have demonstrated early signs of anti-tumor activities in the ongoing GII-101-P101 study1. Here we report clinical outcomes from Part A (GI-101 monotherapy) of the study with additional patients (pts) treated. Methods GII-101-P101 study is a 4-part, first-in-human, phase 1/2 study of GI-101 monotherapy and in combination with various agents in pts with advanced solid tumors. In Part A, dose escalation with 3+3 design established the recommended phase 2 dose (RP2D) and is followed by expansion cohort. Primary endpoints include safety, tolerability and investigator-assessed objective response. Results At the data cut-off of 20 Apr 2023, 57 pts received GI-101 monotherapy (19 in escalation and 38 in expansion cohorts). The median number of prior therapies were 3 [1–11] and 47% were previously experienced immunotherapy. No dose-limiting toxicities (DLTs) were reported in escalation cohort (0.002∼0.3 mg/kg) and maximum tolerated dose (MTD) was not reached. The dose of 0.3 mg/kg GI-101 Q3W was established as the RP2D. Treatment-emergent adverse events (TEAEs) occurred in 55 pts (96%); the most common (>30%) were pyrexia (67%) and transient AST increase (37%). Objective responses were observed in 3/50 evaluable pts regardless of prior anti-PD-(L)1 therapy; 1 confirmed CR (cervical cancer), 1 confirmed PR (UBC) and 1 unconfirmed PR (NSCLC) with 1 CR is ongoing (144+ days). Disease control rate is 46% and median PFS [min-max] was 41 [21-294] days. Meaningful target lesion reduction at 54W (-53%; on-treatment > 429+ days) was observed in MSS CRC with liver metastasis. GI-101 resulted in robust expansion of peripheral lymphocyte at RP2D, median 3.4-fold [2.0-8.4], primarily CD8+ T, NK, effector and central memory T cells, but not Tregs. Lymphocyte expansion was correlated with increased PFS (P=0.00515). Conclusions GI-101 was well tolerated as monotherapy. Monotherapy activity was seen regardless of previous immunotherapy experience, with a favorable benefit to risk profile. The other parts of the trial with pembrolizumab, lenvatinib and radiation continue to enroll.