A Study of AK129 in Patients With Advanced Malignant Tumors

Inclusion Criteria:

1. The subject must sign the written informed consent form(ICF) voluntarily.

2. Aged ≥ 18 to ≤ 75 years.

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

4. Life expectancy≥ 3 months.

5. Histologically or cytologically confirmed advanced solid tumors(dose-escalationphase) or selected tumor species(pharmacodynamic confirmation phase anddose-expansion phase);Patients with advanced metastatic malignancies who have failedfirst-line, or second-line, or third-line, or fourth-line standard therapy, or areineligible for standard therapy, or cannot tolerate chemotherapy, or are unwillingto receive chemotherapy, or have no effective standard therapy.

6. Pharmacodynamic confirmation phase and dose expansion phase: at least one measurabletumor lesion(RECIST v1.1, lymphoma according to Lugano 2014 evaluation criteria).Alesion from a site previously treated with radiotherapy or other local regionaltherapy is considered a non-target lesion unless there is definite progression ofthe lesion or the neoplastic nature of the lesion is confirmed by biopsy.

7. Pharmacodynamic confirmation phase and dose extension phase: All subjects agree toprovide archived or freshly obtained tumor tissue samples within 2 years prior toinitial administration(formalin-fixed paraffin-embedded (FFPE) tissue wax blocks orapproximately 10 unstained tumor tissue sections,and if there is archived tumortissue within 6 months or 3 months, or freshly obtained tumor tissue, preferablyrecently obtained tumor tissue samples).

8. The results of laboratory examination during the screening period indicate that thesubjects have good organ function:1).Hematology (no supportive treatment of anycomponent blood and cell growth factors were used within 7 days prior to the startof the study):Neutrophil absolute value(ANC)≥1.5×10^9/L(solid tumors) or 1.0×10^9/L(lymphoma);Platelet count≥100×10^9/L(solid tumors) or 75×10^9/L(lymphoma);haemoglobin≥90 g/L or ≥5.6 mmol/L. 2).Kidney:Serumcreatinine(Cr)≤1.5×Upper limit of normal(ULN),or Creatinine clearance *(CrCl)calculated value≥ 50 mL/min,CrCl was calculated by Cockcroft-Gault formula:CrCl (mL/min)={(140-age)×weight(kg)×F}/(SCr (mg/dL)×72),Male F=1,Female F=0.85,SCr=serumcreatinine.3).Liver:Serum total bilirubin(TBil)≤1.5×ULN,Subjects withconfirmed/suspected Gilbert disease,TBil ≤ 3× ULN;aspartate aminotransferase(AST)and alanine aminotransferase(ALT) ≤ 2.5×ULN,For subjects with liver metastasis orliver cancer,AST and ALT ≤ 5×ULN.4).Blood clotting function:Internationallystandardized ratio(INR)≤ 1.5×ULN and activated partial thromboplastin time(APTT)≤ 1.5×ULN(If the subject is receiving anticoagulant therapy, the subject will receivea steady dose of anticoagulant and the coagulation parameters(prothrombintime(PT)/INR and APTT) will be within the expected range of anticoagulant therapy atthe time of screening).5).Cardiac function:Left ventricular ejection fraction(LVEF)≥ 50%;Troponin protein T or I<2×ULN.

9. Fertile female subjects must undergo a negative serum pregnancy test within 3 daysprior to initial medication.If a fertile female subject has sex with an unsterilizedmale partner, the subject must initiate a highly effective contraceptive method fromscreening and must agree to continue using these precautions until 120 days afterthe final administration of the study drug;Periodic abstinence, safe periodcontraception and extracorporeal ejaculation are not acceptable contraceptivemethods;

10. If an unsterilized male subject has sex with a fertile female partner, the subjectmust use an effective contraceptive method from the beginning of screening to within 120 days after the last dose.

Exclusion Criteria:

1. Active central nervous system metastasis.

2. Subjects with uncontrolled pleural effusion, pericardial effusion, or abdominaleffusion requiring repeated drainage(frequency greater than monthly).

3. Patients with other active malignant tumors within 2 years prior to the firstadministration, except for locally curable tumor species and those who have beencured, such as squamous cell carcinoma of the skin, basal cell carcinoma of theskin, superficial bladder carcinoma, and carcinoma in situ of the breast.

4. Known primary or secondary immunodeficiency,including human immunodeficiencyvirus(HIV) antibodies tested positive.

5. Known history of allogeneic organ transplantation and allogeneic hematopoietic stemcell transplantation.

6. Known interstitial lung disease or non-infectious pneumonia requiring glucocorticoidtherapy;Except for those caused by radiation therapy.

7. Severe infections, including but not limited to complications requiringhospitalization, sepsis, or severe pneumonia, occur within 4 weeks prior to initialadministration.

8. Present with active infections(including active tuberculosis and active treponemapallidum) requiring systemic treatment, and have used systemic antibacterial,antiviral or antifungal drugs within 2 weeks prior to initial administration;Note:Antiviral drugs for viral hepatitis B are excluded.

9. Subjects with active viral hepatitis B, non-active or asymptomatic hepatitis Bvirus(HBV) carriers(Hepatitis B surface antigen(HBsAg) positive) with HBVdeoxyribonucleic acid(DNA)>200IU/mL, and subjects with active viral hepatitis C.

10. Have active or documented inflammatory bowel disease(e.g. Crohn's disease,ulcerative colitis), active diverticulitis.

11. Any of the following cardiovascular and cerebrovascular diseases:a.Myocardialinfarction, unstable angina pectoris, pulmonary embolism, aortic dissection, deepvein thrombosis, and any arterial thromboembolism events occurred within 6 monthsprior to initial administration;b.New York Heart Association(NYHA) cardiacfunctional grade ≥ II for heart failure;c. Severe arrhythmias requiring long-termdrug intervention; Subjects with asymptomatic and stable ventricular frequency ofatrial fibrillation were admitted.d.Uncontrolled hypertension(defined as systolicblood pressure>150 mmHg and diastolic blood pressure>100 mmHg) with sufficientantihypertensive medication, or a history of hypertensive crisis or hypertensiveencephalopathy.

12. Received the following antitumor drugs or treatments before initialadministration:a. Received monoclonal antibody drugs(including PD-1/L1)immunotherapy drugs within 6 weeks prior to initial administration or within 5half-time period of the drug, whichever is shorter;b. Received small-moleculetargeted drugs, immunomodulatory drugs , Chinese generic drugs with anti-tumorindications, or palliative radiotherapy within 2 weeks prior to initialadministration;c. Received other types of antitumor therapy, including chemotherapy,radical radiotherapy, or any unapproved investigational drug within 4 weeks prior toinitial dosing;d. Major surgical treatment within 4 weeks prior to initialadministration.

13. Dose expansion phase: Immunocheckpoint inhibitors targeting LAG-3 were previouslyused.

14. Subjects requiring therapy with glucocorticoids(prednisone>10 mg/ day or equivalentof glucocorticoids) or other immunosuppressive agents within 14 days prior toinitial administration;The following are excluded:a. Glucocorticoids as prophylacticdrugs for hypersensitivity reactions(such as medication before ComputedTomography(CT) examination).

15. Live vaccine was administered within 4 weeks prior to initial administration.

16. No remission of toxicity from previous antitumor therapy was defined as failure toreturn to National Cancer Institute Common Terminology Criteria for AdverseEvents(NCI CTCAE) v5.0≤1 or the level specified in the inclusion/exclusioncriteria(except hair loss).

17. A known history of severe hypersensitivity to other monoclonal antibodies.

18. Any condition that the investigator believes may result in a risk of receiving thestudy drug or interfere with the evaluation of the study drug or the subject'ssafety or the interpretation of the study results.