KEY TAKEAWAYS
- The phase 1/2 study evaluated the safety and tolerability of GI-101 immunocytokine with pembrolizumab in advanced solid tumors.
- GI-101, in combination with pembrolizumab, showed favorable tolerability and anti-tumor activity in advanced solid tumors, even in patients previously treated with anti-PD(L)1 therapy.
GI-101 (CD80-IL2v) represents a novel immunocytokine directing IL-2v to tumor and immune cells. Engineered for optimal expansion of cytotoxic T and NK cells while inhibiting Treg cells, GI-101 exhibited single-agent activity (ORR 5.9%) in anti-PD-L1 experienced patients.
For this study, researchers evaluated and presented the clinical outcomes from Part B dose escalation. Patients received GI-101 (0.002~0.15 mg/kg) and pembrolizumab (200 mg) intravenously on day 1 of a 21-day cycle. The primary goal is to evaluate safety and tolerability and establish the maximum tolerated dose (MTD) and/or combination recommended phase 2 dose (cRP2D).
As of April 20, 2023, 25 patients with refractory solid tumors received GI-101 plus pembrolizumab. Median prior therapies were 3 [1–9], and 64% had prior immune checkpoint blockade. Treatment-related adverse events occurred in 92%, with pyrexia (48%) and increased AST/ALT (28%, 24%) being the most common. Dose-limiting toxicity occurred once, and MTD was not reached.
The cRP2D is 0.15 mg/kg GI-101 Q3W, showing desirable immune cell expansion and anti-cancer activities. Objective responses occurred in 16.7% of 24 evaluable patients, with 2 confirmed PR in NSCLC and ccRCC and 2 unconfirmed PR in MUO and ccRCC. ORR in ICI-experienced patients was 13.3%, while ICI-naïve patients had a 22.2% ORR. The DCR was 66.7%, including 4 SD > 6 months.
Responders exhibited higher central memory T and CD8+ T cell levels. In a patient achieving PR, significant CD8+ T and NK cell infiltration occurred in the tumor microenvironment, with minimal impact on Treg cells.
The combination of GI-101 and pembrolizumab proved well-tolerated in patients with advanced solid tumors, showing anti-tumor activity in heavily pre-treated individuals with prior anti-PD(L)1 therapy. The study’s dose expansion phase is currently underway.
Source: https://jitc.bmj.com/content/11/Suppl_1/A805
Clinical Trial: https://clinicaltrials.gov/study/NCT04977453
Cho BC, Lee JL, Shin SJ, et al710 Keynote-B59: dose escalation of a phase 1/2 first-in-human, open-label study of GI-101, a novel immunocytokine combining CD80-IL2v, in combination with pembrolizumab in advanced solid tumorsJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0710
