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Objective: GI-101 (CD80-IL2v) is an innovative immunocytokine designed to direct IL2v to tumor and immune cells. The IL2v of GI-101 is engineered to enhance the expansion of cytotoxic T and natural killer (NK) cells but not regulatory T (Treg) cells, and CD80 further inhibits immunosuppressive function of Treg cells. Early data from phase 1/2 study was presented at European Society for Medical Oncology 2023; in 61 patients who received GI-101, monotherapy activity was confirmed with great safety and tolerability. GI-101 induced significant expansion of lymphocytes, CD8+ T and NK cell, which was correlated with prolonged progression-free survival. Here, we present results of patients with gynecological cancer enrolled in Part A of GII-101-P101 (KEYNOTE-B59, NCT04977453). Methods: This study is an ongoing phase 1/2 study of GI-101 monotherapy and its combination with various agents in patients with advanced/metastatic solid tumors. In Part A, dose escalation using a 3+3 design (0.002-0.3 mg/kg; every 3 weeks) established the recommended phase 2 dose of GI-101 at 0.3 mg/kg, followed by an expansion cohort. The primary endpoint was safety, tolerability and investigator-assessed objective response. Results: At the data cut-off of 21 January 2024, 10 patients with gynecologic cancer who had previously failed standard of care, 5 patients with metastatic cervical cancer (mCC), a patient with metastatic endometrial cancer (mEC) and 4 patients with metastatic ovarian cancer. received 0.3 mg/kg of GI-101. Patients were aged 39-72 years and were all Asian (n=10), had an Eastern Cooperative Oncology Group performance status of 0 (n=8) or 1 (n=2), and had a median of 3 prior lines of therapy (LoT, range: 1-10), including immune checkpoint blockade (ICB; n=4). Frequent (=50%) treatment-related adverse events were pyrexia (80%) and increased aspartate aminotransferase (80%) and alanine aminotransferase (70%), Among 10 patients, 1 confirmed complete response (cCR) and 1 unconfirmed partial response (uPR) were observed in mCC and mEC, respectively. The patient with mCC received 2 prior LoT, including ICB, and had tumor characteristics of proficient mismatch repair (pMMR) and programmed cell death ligand 1 (PD-L1) Combined positive score (CPS) 70. CR was observed after 2 cycles of GI-101, and the response was maintained for 12.4+ months (treatment duration 13.8+ months), indicating durable response induced by GI-101. Immune cell analysis revealed that the patient showed significant expansion of total lymphocytes, NK, CD8+ T and central memory T (Tcm) cells, 2.9, 1.9, 1.4, and 2.6-fold increase from baseline, respectively. The patient with mEC had multiple lung metastases and failed on 2 prior LoT, with tumor characteristics of pMMR, wild type p53 and PD-L1 CPS 35. After GI-101 treatment, the patient maintained stable disease (SD) for 8.2 months and the tumor turns to reduce by -36 % from 9.7 month of the treatment, evaluated as uPR (treatment duration 11.5+ months). The patient's peripheral blood showed robust expansion of total lymphocytes, NK, CD8+ T and Tcm cells (2.8, 5.7, 2.5, and 2.8-fold change from baseline, respectively). In 4 ovarian cancers with a median 5 prior LoT (range: 3-10), all patients' best target lesion reduction is assessed as SD showing 100% disease control rate. Conclusion: GI-101 was generally well-tolerated and provided evidence of tumor response and disease control in patients with gynecological cancer, regardless of previous anti-PD(L)1 therapies. The response kinetics showed both immediate and delayed tumor reduction after GI-101 treatment. Further exploration for new therapeutic option utilizing GI-101 in gynecological cancer is warranted. [ABSTRACT FROM AUTHOR]