Dose escalation of KY-0118, PD-1, and IL-2v due-target fusion protein in patients with advanced renal clear cell carcinoma, urothelial carcinoma, and malignant melanoma.

e14505 Background: KY-0118 is an anti-PD1 and IL-2v(variant) fusion protein for advanced solid tumors. The non-α biased design reduces the binding to IL2-Raβγ and enhanced binding to PD-1 & IL2-Rβγ positive TILs to drive increased proliferation and activation of NK and CD8 + T cells without unwanted expansion of Tregs. KY-0118 adopts specific single design, only 67kDa MW thus obtains excellent tumor penetration activity. The preclinical data shows higher antitumor activity in several CDX models compared with nivolumab and IL2wt. KY-0118 monotherapy is currently in Phase I escalation. Methods: The phase I dose escalation is a traditional 3+3 design, KY-0118 on Days 1, 8 and 15, 21-day treatment cycle, 9 dose levels (0.3μg/kg-64μg/kg) or higher doses of 3 to 6 patients are planned. The dose expansion cohort is currently enrolling. The primary endpoint was to evaluate the safety, tolerability, and determine the DLT, MTD, RP2D of KY 0118 when given alone. Secondary objectives are PK/PD characteristics and preliminary evidence of efficacy via ORR per RECIST v1.1 and iRECIST. Results: Up to Jan 31, 2024, 21 patients have been treated, the median number of prior lines of systemic therapy was 2. The dose level 8 (48µg/kg) of DLT observation period is ongoing, no DLT was observed in the administered dose groups. Most of TEAEs are transient grade 1-2, no TEAE led to withdrawal from this study. The most common nonhematologic TRAEs were pyrexia, flu-like symptoms, nausea, fatigue. 2 patients had grade 3 hematologic toxicity. Treatment-related sAEs were observed in one patient (include nausea, vomiting, and pulmonary embolism, now recovered and continuing treatment). No patients experienced complete or partial response, but several showed evidence of antitumor activity, at the dose of 36 ug/kg, 21% shrinkage of target lesions in a patient with RCC, the DCR for the 12, 24, and 36μg/kg dose levels are 33%, 75%, and 67%, respectively. Conclusions: These preliminary data suggest that KY-0118 demonstrated a manageable safety profile and encouraging early evidence of activity has been observed in locally advanced and/or metastatic solid tumors. Enrollment is ongoing, further results are forthcoming. Pts: 21; AEs: 399; TEAEs: 289 (100%); AESI: 13; sAEs: 8. Clinical trial information: NCT06175780 .