A Clinical Study to Evaluate the Safety of VIB305 in Patients With Advanced Solid Tumors

An Open-label, Dose-escalation and Dose-expansion Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic (PK) Characteristics, and Preliminary Efficacy of VIB305 in Patients With Advanced Solid Tumors

This clinical trial is an open-label, single-arm, non-randomized, dose-escalation and dose-expansion study targeting subjects with unresectable, advanced, malignant solid tumors who have failed or are unsuitable for standard treatments or refused the existing treatments.

This study is divided into a dose-escalation phase (Phase I) and a dose-expansion phase (Phase II). Phase I (dose escalation) is designed to preliminarily evaluate the safety and tolerability of VIB305 in advanced solid tumors, to determine the nature and incidence of dose-limiting toxicities (DLTs), and thereby to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Based on the findings from the Phase I portion for evaluation in the Phase II portion. Phase II (dose expansion) will enroll additional cohorts to further assess the safety and tolerability, PK profile, preliminary antitumor activity and immunogenicity of VIB305 in specific tumor types (selected based on all available data).

Inclusion Criteria:

1. Aged ≥18 years, male or female.
2. Subjects with histologically or cytologically confirmed advanced solid tumors that are unresectable, who are refractory to or intolerant of or refuse all existing therapy(ies) known to provide clinical benefit for their condition.
3. At least one measurable lesion as assessed by RECIST 1.1.
4. ECOG performance status score of 0-1.
5. Estimated survival time of more than 3 months.
6. Adequate organ function.
7. Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to first administration of the investigational drug. Females of childbearing potential must agree to abstain or use highly effective contraception from the time of signing informed consent form until 6 months after their last dose of the investigational drug.
8. Male subjects of reproductive capacity must agree to use effective contraception from the time of signing informed consent form until 6 months after their last dose of the investigational drug.
9. Subjects must be fully informed about this study before participation and must voluntarily sign a written informed consent form.

Exclusion Criteria:

1. Receipt of chemotherapy, biotherapy, endocrine therapy, immunotherapy, or other systemic anti-tumor therapy within 4 weeks prior to first dose of investigational drug.
2. Receipt of radiotherapy within 4 weeks prior to initiation of study treatment, or history of radiation pneumonitis.
3. Receipt of any other investigational drugs not yet marketed within 4 weeks prior to first dose of investigational drug.
4. Receipt of major organ surgery or occurrence of significant trauma, or requirement for elective surgery during the study, within 4 weeks prior to first dose of investigational drug.
5. Use of systemic glucocorticoids or other immunosuppressive agents within 14 days prior to the first dose of investigational drug or anticipated need during the study.
6. Use of immunomodulatory agents, including but not limited to thymosin, interleukin-2, interferons, etc., within 14 days prior to first administration of investigational drug.
7. Receipt of live vaccine or attenuated live vaccine within 4 weeks prior to first use of investigational drug. Inactivated vaccines are permitted.
8. History of prior allogeneic bone marrow transplantation or organ transplantation.
9. Adverse reactions from prior anti-tumor therapy have not recovered to ≤ Grade 1 based on CTCAE v5.0.
10. Subjects with central nervous system (CNS) metastasis.
11. Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose.
12. Known history of human immunodeficiency virus (HIV) positivity or history of acquired immunodeficiency syndrome (AIDS).
13. Subjects with active hepatitis B virus (HBV) infection.
14. History of other malignancies within the past 5 years.
15. History of severe cardiovascular or cerebrovascular disease.
16. Clinically significant severe pulmonary dysfunction.
17. Subjects with active or recurrent autoimmune diseases, or a related history and high risk for recurrence, or subjects at high risk.
18. Subjects with ulcerative keratitis, acute keratitis, or progressive keratitis.
19. Subjects with severe skin diseases.
20. Known hypersensitivity or allergy to any component of the investigational drug.
21. Prior receipt of immunotherapy, with severe immune-related toxicity regardless of remission status, as determined by the investigator to be unsuitable for immunotherapy.
22. Clinically uncontrolled pericardial, pleural, or peritoneal effusions requiring repeated drainage.
23. Dementia or altered mental status that may impair understanding and provision of informed consent form.
24. Pregnant or lactating females.
25. Underlying conditions.
26. Prior receipt of treatment with T cell engager drugs containing CD3 monoclonal antibodies.