A Phase Ia/Ib Open Label，Clinical Study Evaluating the Safety, Tolerability and Preliminary Efficacy of AK127 in Combination With AK104 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,male and female at the time of enrollment. 3.Eastern CooperativeOncology Group(ECOG) performance status score of 0 or 1. 4.Life expectancy≥ 3months. 5.Patients with histologically or cytologically confirmed advanced,recurrent, or metastatic malignancies were enrolled in the phase Ia dose escalationphase;Selected tumor species were enrolled in phase Ib dose extension.Patients withadvanced metastatic malignancies who have failed first-line, or second-line, orthird-line, or fourth-line standard therapies, or who not appropriate for standardtreatment, cannot tolerate chemotherapy, or do not have effective standardtherapies.

6. According to RECIST v1.1, there is at least one measurable lesion, and thelesion is suitable for repeated accurate measurement;Brain metastases cannot beused as target foci.

7. Good organ function. 8. The serum pregnancy test results of female subjects inthe child-bearing age within 3 days before the first medication were negative;

8. If a fertile female subject has sex with an unsterilized male partner, thesubject must begin from screening for effective contraceptive methods and mustagree to continue using these precautions until 6 months after the lastadministration of the study drug;Periodic abstinence, safe period contraceptionand external ejaculation are not acceptable contraceptive methods.

9. If an unsterilized male subject has sexual intercourse with a fertile femalepartner, the subject must use an effective contraceptive method from thebeginning of screening to within 6 months after the last dose.

Exclusion Criteria:

1. Previous treatment for:Use of small-molecule targeted antitumor drugs,monoclonal or double-clonal antibodies targeting PD-(L)1 or CTLA-4, otheranti-tumor antibodies, other anti-tumor therapies (e.g., chemotherapy,radiotherapy, biological or hormonal therapy) within 4 weeks prior to initialadministration of the study drug, previous use of immunomodulatory drugs within 2 weeks prior to initial administration of the study drug,Prior treatment withapproved or investigational TIGIT antibodies, PVRIG antibodies, or CD96antibodies.

2. Enroll in another clinical study at the same time. 3. Received other antitumortherapy 4 weeks before the first administration or 5 half-lives of the drug (whichever is shorter) : e.g. palliative local therapy for non-target lesionswas performed within 2 weeks before the first administration;Receivednon-specific immunomodulatory therapy within 2 weeks prior to initialadministration;Received Chinese herbal medicine or Chinese patent medicine withanti-tumor indications within 1 week prior to initial administration.

3. Central nervous system metastasis with clinical symptoms. 5. Other malignancieswithin 3 years prior to the first medication. 6. Active autoimmune diseaserequiring systemic treatment within 2 years prior to initial medication.

4. History of serious disease within 1 year before the first medication. 8.History of gastrointestinal perforation and/or fistula, history ofgastrointestinal obstruction, and extensive enterectomy within 6 months priorto initial administration.

5. Patients receiving chest radiotherapy >30 Gy within 6 months before the firstdrug use, non-chest radiotherapy >30 Gy within 4 weeks before the first druguse, and palliative radiotherapy ≤30 Gy within 2 weeks before the first druguse.Subjects who did not recover from toxicity and/or complications from theseinterventions to NCI CTCAE grade ≤1 (except hair loss and fatigue).

6. Live or attenuated vaccine has been administered within 4 weeks prior toinitial administration, or if it is planned to be administered during the studyperiod. Inactivated vaccine is permitted .

7. Severe infection occurs within 4 weeks prior to first dosing. 12. Those whohave had major surgical operations or severe trauma within 4 weeks prior to thefirst dosing, or have major surgical operations planned within 4 weeks afterthe first dosing; Minor local surgery was performed within 3 days prior tofirst dosing.

8. History of severe bleeding tendency or coagulopathy;There were clinicallysignificant bleeding symptoms, including but not limited to gastrointestinalbleeding, hemoptysis, and nasal bleeding, within 4 weeks prior to first dosing .

9. Systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg afteroral antihypertensive medication with present hypertension.

10. Hyperglycemia that has not been controlled by treatment. 16. Pleural effusion,pericardial effusion or ascites with clinical symptoms or requiring repeateddrainage.

11. There is a history of noninfectious pneumonia requiring systemic glucocorticoidtherapy or a current interstitial lung disease.

12. Active or have a clear history of inflammatory bowel disease. 19.History ofimmune deficiency; HIV antibody positive; Systemic corticosteroid hormones orother immunosuppressants are currently being used long-term.

13. Known history of allogeneic organ transplantation and hematopoietic stem celltransplantation.

14. Untreated subjects with active hepatitis B;Active hepatitis C subjects. 22. Noremission of toxicity from previous antitumor therapy, defined as failure toreturn to the grade 1 level of toxicity defined in NCI, CTCAE 5.0 or below, orthe inclusion/exclusion criteria, with the exception of alopecia and fatigue.

15. Known allergy to any component of any study drug; known history of severehypersensitivity to other monoclonal antibodies.