a study to evaluate yh001 in subjects with advanced solid tumors

Conditions: Advanced Solid Tumors

Summary: 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).

Eligibility criteria:
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.