A Study to Evaluate YH001 in Subjects With Advanced Solid Tumors

A Open-Label, Phase I Dose Escalation Study to Evaluate the Safety, Tolerability,Efficacy and Pharmacokinetics of YH001 in Subjects With Advanced Solid Tumors

This is an open-label, dose-escalation study of the study drug YH001 . The study is designed to determine the safety, tolerability and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of YH001 in subjects with advanced solid tumors.

This is a single arm clinical trial in subjects with advanced solid tumor receiving multiple doses of YH001 intravenously (IV). YH001 will be administered (IV) in 19-37 patients with advanced solid tumors. An accelerated titration method followed by a traditional 3+3 dose escalation scheme will be utilized to determine MTD(maximum tolerated dose) and/or RP2D(recommended phase 2 dose). Patients will be dosed at Dose A, Dose B, Dose C, Dose D, Dose E, Dose F and Dose G every 3 weeks (Q3W) for 15 weeks (5 cycles).

Inclusion Criteria:

1. Male or female, aged ≥ 18 years;

2. Patients with histologically or cytologically confirmed solid tumors who have failed standard of care or have no standard of care;

3. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1;

4. Have life expectancy of at least 3 months based on investigator's judgement;

5. Organ function levels must meet the following requirements:

   A:Hematology: absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet count ≥ 100 x 10^9/L, hemoglobin (Hb) ≥ 100 g/L ; B:Liver: serum total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (patients with primary liver cancer or liver metastases: AST and/or ALT < 5 × ULN); C:Kidney: creatinine clearance (CrCL) ≥ 50 mL/min;

6. International normalized ratio (INR) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN, activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN;

7. All women of reproductive potential, men whose partner is a woman of reproductive potential, or their spouses should use adequate barrier contraception throughout the study and for 3 months after the last dose;

8. Voluntary and agree to sign the informed consent and follow the study treatment protocol as well as follow-up plan.

Exclusion Criteria:

1. Subjects with prior anti-CTLA-4 checkpoint inhibitors should be excluded;

2. Patients with any other malignancy within the past 5 years or currently, except for completely cured non-melanoma skin cancer, carcinoma in situ of the cervix, and ductal carcinoma in situ of the breast;

3. Received other anti-tumor therapies (such as chemotherapy, radiotherapy, surgery, endocrine therapy, targeted therapy, immunotherapy, etc.) within 4 weeks or 5 half-lives (whichever is longer) before the first dose, or received modern Chinese medicine preparations with anti-tumor effect approved by NMPA within 2 weeks prior to the first dose;

4. Major surgery (excluding vascular access establishment surgery) was received within 4 weeks prior to the first dose;

5. Has received immunosuppressive therapy within 4 weeks prior to the first dose. However, enrollment is permitted under the following circumstances:

6. In the absence of active autoimmune disease, patients are allowed to receive inhaled or topical glucocorticoids, or other glucocorticoids at doses ≤ 10 mg/day prednisone equivalent.

   Patients with primary central nervous system (CNS) tumors, or symptomatic CNS tumors, or spinal cord compression, or carcinomatous meningitis; with the following exceptions:

   Patients with asymptomatic brain metastases (i.e., no progressive central nervous system symptoms due to brain metastatic sites, no need for corticosteroids, and lesion size ≤ 1.5 cm); Patients whose symptoms are controlled by treatment, i.e., their condition is stable and asymptomatic at least 4 weeks after treatment;

7. Use of any other study drug within 4 weeks prior to the first dose, or participation in other clinical studies;

8. Have received live or attenuated vaccines within 4 weeks prior to the first dose;

9. Patients with known severe allergic reactions (≥ Grade 3) to the active ingredient and excipients of the investigational drug, other monoclonal antibodies or "Immuno-oncology drugs;

10. Toxic and side effects caused by prior anti-tumor therapy before the first dose did not recover to ≤ Grade 1 (CTCAE v5.0), except for alopecia and sensory neuropathy below Grade 2;

11. History of interstitial pneumonia or non-infectious pneumonitis requiring corticosteroids, except for radiation therapy, or current presence of interstitial pneumonia or non-infectious pneumonitis;

12. ≥ Grade 2 immune-related pneumonitis occurred during prior immunotherapy;

13. History of ≥ Grade 3 immune-related adverse reactions or any adverse reactions leading to discontinuation of immunotherapy during prior immunotherapy;

14. Past or existing active tuberculosis ;

15. Patients with active auto-immune disease, history of auto-immune disease requiring systemic therapy, or history of auto-immune disease within 2 years prior to the first dose, with the following exceptions: leucoderma, childhood asthma/specific reactions, type I diabetes mellitus, hypothyroidism which can be treated with replacement therapy;

16. Clinically uncontrollable disease, including, but not limited to, severe diabetes (fasting glucose > 250 mg/dl,1 mg/dl = 18 mmol/L), uncontrollable hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg), or other serious disease requiring systemic treatment;

17. Patients with active infections, including active hepatitis B, active hepatitis C, and human immunodeficiency virus infection;

18. Patients with active infection requiring intravenous infusion;

19. Serious cardiovascular and cerebrovascular diseases, such as cerebrovascular rupture, stroke, myocardial infarction, unstable angina pectoris, congestive heart failure (New York Heart Association Grade ≥ II), severe uncontrolled arrhythmia, etc., occurred within 6 months prior to the first dose;

20. Patients with clinically significant ECG abnormalities: QTcF ≥ 470 msec (corrected by Fridericia), or having history of congenital long QT syndrome, or taking any known QTc prolonging medication;

21. Patients who have received allogeneic bone marrow transplant or organ transplant;

22. Known psychiatric disorders, drug abuse, drug use, or alcohol dependence that may affect trial compliance;

23. Other conditions that were considered not suitable for the study by the investigator.