1027P - 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)

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.

Clinical trial identification

NCT04977453.

Editorial acknowledgement

Legal entity responsible for the study

GI Innovation, Inc.

Funding

GI Innovation, Inc. Korea Drug Development Fund.

Disclosure

All authors have declared no conflicts of interest.