Shim, Byoung Yong

2598 Background: GI-102 (CD80-IL2v3) is a novel immunocytokine designed to direct IL-2v3 to immune cells and tumor cells. IL-2v3 of GI-102 abolished affinity to IL-2Rα minimizing the impact of IL-2 on Treg cells. Preferential targeting of immune cells and further inhibition of CTLA-4 and PD-L1 via CD80 synergize with potent activity of IL-2v3, resulting in robust proliferation and activation of CD8+ T and NK cells. Here we report preliminary safety and efficacy data of GI-102 from a phase 1/2a trial in patients with metastatic solid tumors. Methods: NCT05824975 is an ongoing, dose escalation (3+3 design) and expansion study to evaluate safety, tolerability, PK, PD and anti-tumor activity of GI-102. Each dose level allows to enroll additional 7 patients to fully inform the safety, PK and PD at that dose level. GI-102 was administered intravenously every 3 weeks until disease progression or unacceptable toxicities. Disease was assessed every 6 weeks using RECIST v1.1. Results: As of 12 Jan 2024, 32 patients were treated in dose escalation: 8 at dose level 0.06 mg/kg, 10 at 0.12 mg/kg, 9 at 0.24 mg/kg and 5 at 0.45 mg/kg. Patients had received median of 3 [1-7] prior lines of therapy, including 25.0% (8/32) who had received ≥ 5 lines and 68.8% (22/32) had experienced immune checkpoint blockade (ICB). No dose-limiting toxicities (DLTs) were observed until the highest dose of 0.45 mg/kg Q3W. The most common treatment-related adverse events (TRAEs, ≥ 10%) were pyrexia [43.8%] and chills [34.4%]. 5 patients [15.6%] had ≥ Grade 3 TRAEs and no patient reported TRAEs leading to discontinuation of GI-102. In 23 patients (7 cutaneous melanoma, 4 non-small cell lung cancer, 3 ovarian cancer and others) who had at least 1 post-treatment tumor assessment, objective responses were observed in 17.4% (4/23). In patients with metastatic melanoma who previously experienced ICB, overall response rate (ORR) and disease control rate (DCR) was 42.9% (3/7) and 85.7% (6/7), respectively, including 3 confirmed partial responses (cPR). The median time to response (TTR) was 6 weeks and duration of response (DoR) was 6.0+, 2.4+ and 1.7+ month, respectively. In patients with metastatic ovarian cancer, ORR and DCR were 33.3% (1/3) and 66.7% (2/3), respectively, including 1 cPR [TTR of 6 weeks; DoR 1.9+ month]. Preliminary PK profile showed target-mediated drug disposition with a half-life of ~48 hours. 0.24 mg/kg of GI-102 resulted in a significant expansion of peripheral lymphocytes, CD8+ T cells (effector & memory) and NK cells, by 4.4 [2.1-9.6], 3.9 [2.0–5.7] and 20.4 [9.5–32.6]-fold change from baseline, respectively. There was no meaningful increase in Treg cells. Conclusions: GI-102 was well tolerated up to dose of 0.45 mg/kg Q3W with meaningful monotherapy activity, regardless of previous ICB experience, in patients who failed on standard of care. The dose-escalation is currently ongoing to identify RP2D. Clinical trial information: NCT05824975 .

31 Background: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) inhibitor in combination with an anti-programmed cell death protein 1 (PD-1) antibody has shown antitumor activity in solid tumors. AdvanTIG-105 (NCT04047862) is a phase 1/1b open-label study designed to assess the safety and preliminary antitumor activity of OCI, an anti-TIGIT monoclonal antibody (mAb), + TIS, an anti-PD-1 mAb, in pts with unresectable, locally advanced or metastatic solid tumors. In the dose-escalation part, OCI + TIS was well tolerated with preliminary antitumor activity observed, and the recommended phase 2 dose (RP2D) of OCI 900 mg intravenously (IV) every three weeks (Q3W) + TIS 200 mg IV Q3W was established. We report results from the dose-expansion part (GC/GEJC Cohort 9) of the AdvanTIG-105 study. Methods: Eligible pts had histologically/cytologically confirmed stage IV GC/GEJC. Pts were excluded if they had squamous cell, undifferentiated or other histological types of GC, had GC/GEJC with positive HER2 expression, or if they had received any prior therapy for metastatic disease. Pts received either the RP2D of OCI + TIS with oxaliplatin + capecitabine Q3W for 6 cycles (C), followed by maintenance therapy with the RP2D of OCI + TIS, + capecitabine Q3W, or the RP2D of OCI + TIS with cisplatin + 5-fluorouracil Q3W for 6 C. Treatment continued until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed overall response rate (ORR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DoR), disease control rate (DCR) per RECIST v1.1, and safety. Results: As of September 29, 2022, 60 pts with a median age of 61.5 years (range 35-82) were enrolled; 59 were efficacy evaluable. Median study follow-up was 31.1 weeks (range 1.4-78.4). ORR was 50.8% (95% CI: 37.5, 64.1); DCR was 84.7% (95% CI: 73.0, 92.8) with a median DoR of 8.1 months (95% CI: 4.5, not evaluable [NE]). Median PFS was 8.2 months (95% CI: 5.8, NE). In a subgroup analysis, ORR in pts with PD-L1 tumor area positivity (TAP) score ≥5% (n=27) was 59.3% (95% CI: 38.8, 77.6), and 50.0% (95% CI: 30.7, 69.4) in pts with PD-L1 TAP <5% (n=28). All 60 pts reported ≥1 treatment-emergent adverse event (TEAE), the most common being anemia (43.3%) and platelet count decreased (41.7%). In total, 43 pts (71.7%) had ≥grade 3 TEAEs and 28 (46.7%) had serious adverse events. TEAEs leading to discontinuation of TIS and OCI occurred in 5 (8.3%) pts. TEAEs led to death in 2 (3.3%) pts; one event (neutropenic sepsis) was related to chemo, while the other (pulmonary embolism) was not treatment related. Conclusions: OCI 900 mg + TIS 200 mg + chemo was generally well tolerated and showed encouraging antitumor activity in pts with stage IV GC/GEJC. Clinical trial information: NCT04047862 .

4028 Background: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) inhibitor in combination with an anti-programmed cell death protein 1 (PD-1) antibody has shown antitumor activity in solid tumors. AdvanTIG-105 (NCT04047862) is a phase 1/1b open-label study designed to assess the safety and preliminary antitumor activity of OCI, an anti-TIGIT monoclonal antibody (mAb), + TIS, an anti-PD-1 mAb, in pts with unresectable, locally advanced or metastatic solid tumors. In the dose-escalation part, OCI + TIS was well tolerated with preliminary antitumor activity observed, and the recommended phase 2 dose (RP2D) of OCI 900 mg intravenously (IV) every three weeks (Q3W) + TIS 200 mg IV Q3W was established. We report results from the dose-expansion part (GC/GEJC Cohort 9) of the AdvanTIG-105 study. Methods: Eligible pts had histologically/cytologically confirmed stage IV GC/GEJC. Pts were excluded if they had squamous cell, undifferentiated or other histological types of GC, had GC/GEJC with positive HER2 expression, or if they had received any prior therapy for metastatic disease. Pts received either the RP2D of OCI + TIS with oxaliplatin + capecitabine Q3W for 6 cycles (C), followed by maintenance therapy with the RP2D of OCI + TIS, + capecitabine Q3W, or the RP2D of OCI + TIS with cisplatin + 5-fluorouracil Q3W for 6 C. Treatment continued until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed overall response rate (ORR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DoR), disease control rate (DCR) per RECIST v1.1, and safety. Results: As of September 29, 2022, 60 pts with a median age of 61.5 years (range 35-82) were enrolled; 59 were efficacy evaluable. Median study follow-up was 31.1 weeks (range 1.4-78.4). ORR was 50.8% (95% CI: 37.5, 64.1); DCR was 84.7% (95% CI: 73.0, 92.8) with a median DoR of 8.1 months (95% CI: 4.5, not evaluable [NE]). Median PFS was 8.2 months (95% CI: 5.8, NE). In a subgroup analysis, ORR in pts with PD-L1 tumor area positivity (TAP) score ≥5% (n = 27) was 59.3% (95% CI: 38.8, 77.6), and 50.0% (95% CI: 30.7, 69.4) in pts with PD-L1 TAP < 5% (n = 28). All 60 pts reported ≥1 treatment-emergent adverse event (TEAE), the most common being anemia (43.3%) and platelet count decreased (41.7%). In total, 43 pts (71.7%) had ≥grade 3 TEAEs and 28 (46.7%) had serious adverse events. TEAEs leading to discontinuation of TIS and OCI occurred in 5 (8.3%) pts. TEAEs led to death in 2 (3.3%) pts; one event (neutropenic sepsis) was related to chemo, while the other (pulmonary embolism) was not treatment related. Conclusions: OCI 900 mg + TIS 200 mg + chemo was generally well tolerated and showed encouraging antitumor activity in pts with stage IV GC/GEJC. Clinical trial information: NCT04047862 .