Study of GV20-0251 in Participants With Solid Tumor Malignancies

This is a Phase 1/2A non-randomized, open-label, multi-center study to be conducted in 2 parts (A and B).

Part A is a safety run-in portion. A 3+3 dose escalation scheme will be used to evaluate the safety and tolerability of GV20-0251, and to establish the maximum tolerated dose (MTD) or the preliminary recommended Phase 2 dose (RP2D).

In Part B, the Simon 2-stage design will be utilized to further characterize the anti-tumor activities, safety, tolerability, pharmacokinetics, and pharmacodynamics of GV20-0251 at the preliminary RP2D across multiple expansion cohorts involving eligible participants.

Inclusion criteria

• Before conducting any study-specific procedures, voluntarily sign an informed consent form.
• Be able and willing to participate throughout the entire study period and comply with study procedures.
• participants ≥18 years of age
• Previously treated, histologically-confirmed advanced solid malignancy with progressive disease requiring therapy (Refractory or intolerant to standard therapies, must have received the standard of care therapy)
• Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)
• For participants who have received prior treatment with a checkpoint inhibitor there must be documented disease progression
• ECOG performance status of 0 or 1 before C1D1
• Part B Participants must be willing to provide fresh tumor biopsy (core biopsy) both pre-treatment and on-treatment, if clinically feasible
• Disease-free of active second/secondary or prior malignancies for ≥ 2 years Laboratory test results within the required parameters
• Women of childbearing potential (WOCBP) and men must agree to use adequate contraception

Exclusion criteria

• Participants with acute leukemia or CLL
• Participant with heart disease (NYHA ≥ Level II), myocardial infarction within the past 6 months, or unstable arrhythmia
• Fridericia-corrected QT interval (QTcF) > 470 msec, or the presence of congenital long QT syndrome, or a history of clinically significant electrocardiogram (ECG) abnormalities (including pericarditis) that, in the investigator's judgment, may affect the subject's safety.
• Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy within 7 days before C1D1
• Participant has active autoimmune disease or other medical conditions requiring chronic systemic steroid or immunosuppressive therapy
• Known human immunodeficiency virus (HIV) infection, known hepatitis B virus (HBV), or hepatitis C virus (HCV) infection, unless meeting the specific conditions.
• History of major organ transplant and/or a bone marrow transplant
• Symptomatic central nervous system (CNS) malignancy or metastasis
• Serious nonmalignant disease
• Pregnant or nursing women
• Major surgery within 28 days prior to the first dose of study medication
• Prior anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) before the first dose of GV20-0251 on Cycle 1 Day 1 (C1D1), with the exceptions.
• History of severe allergic reactions to biologic therapy, which in the investigator's judgment may increase the subject's risk.
• Radiation therapy for symptomatic lesions within 14 days prior to C1D1 dosing.
• Active substance abuse
• Any history of an immune-related ≥ Grade 3 AE attributed to prior cancer immunotherapy