A Study of IMM2510 + IMM27M Combination Therapy in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. The patient can understand the procedures and methods of this clinical trial. Aftergiving full informed consent, the patient voluntarily participates in it and signsthe informed consent form.

2. Aged between 18 and 75 years old (including both ends), regardless of gender.

3. Clinical diagnosis: Dose escalation phase: Patients with advanced malignant solid tumors confirmed byhistology or cytology, who have failed previous standard treatments, have nostandard treatment regimens or are not suitable for standard treatment at present,including but not limited to hepatocellular carcinoma, triple-negative breastcancer, soft tissue sarcoma, non-small cell lung cancer, epithelial ovarian cancer,small cell lung cancer, malignant melanoma, colorectal cancer, ovarian cancer,endometrial cancer, renal cell carcinoma, squamous cell carcinoma of the head andneck, etc. Dose expansion phase: The following tumor types are included: a. Patients withadvanced hepatocellular carcinoma who have failed or could not tolerate at least oneline of previous systemic treatment; b. Patients with locally advanced, unresectableor metastatic triple-negative breast cancer confirmed by histology or cytology, whohave failed or could not tolerate at least one line of previous systemic treatment;c. Patients with other advanced malignant solid tumors (except those withtriple-negative breast cancer and advanced hepatocellular carcinoma) confirmed byhistology or cytology, who have failed or could not tolerate at least one line ofprevious systemic treatment, including but not limited to soft tissue sarcoma,non-small cell lung cancer, epithelial ovarian cancer, small cell lung cancer,malignant melanoma, colorectal cancer, ovarian cancer, endometrial cancer, renalcell carcinoma, squamous cell carcinoma of the head and neck, etc.

4. Dose escalation phase: According to RECIST version 1.1, there should be at least oneevaluable tumor lesion; Dose expansion phase: According to RECIST version 1.1, thereshould be at least one measurable tumor lesion.

5. ECOG performance status score of 0 - 1.

6. The expected survival time is more than 3 months.

7. There should be sufficient organ function. Hematological system (without receivingblood transfusion or hematopoietic stimulating factor treatment within 14 days):Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, Platelet count (PLT) ≥ 100 × 10⁹/L,Hemoglobin (Hb) ≥ 90 g/L. For patients with HCC accompanied by liver cirrhosis, ANC ≥ 1.0 × 10⁹/L and platelet count ≥ 90 × 10⁹/L are acceptable for enrollment. Liver function: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN), forpatients with liver metastasis or liver cancer, TBIL ≤ 3.0 × ULN; Alanineaminotransferase (ALT) ≤ 2.5 × ULN, for patients with liver metastasis or livercancer, ALT ≤ 5.0 × ULN; Aspartate aminotransferase (AST) ≤ 2.5 × ULN, for patientswith liver metastasis or liver cancer, AST ≤ 5.0 × ULN. Renal function: Creatinine clearance rate (Ccr) ≥ 50 ml/min (calculated according tothe Cockcroft-Gault formula), Urinary protein < 2+ or 24-hour urinary proteinquantification < 1.0 g. Coagulation function: Prothrombin time (PT) ≤ 1.5 × ULN, Activated partialthromboplastin time (APTT) ≤ 1.5 × ULN, International normalized ratio (INR) ≤ 1.5 ×ULN. Cardiac function: 12-lead electrocardiogram, QTc interval ≤ 480 ms, Echocardiogram,Left ventricular ejection fraction (LVEF) ≥ 50%. Thyroid function: Thyroid-stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 andFT4 levels should be observed simultaneously. If FT3 and FT4 levels are normal,enrollment is allowed). Liver function grading for HCC patients: Child-Pugh score ≤ 7 points.

8. Qualified patients (both male and female) with fertility must agree to use reliablecontraceptive methods (hormonal or barrier methods or abstinence) together withtheir partners during the trial period and at least 6 months after the lastadministration.

9. The patient must be informed of this study before the trial and voluntarily sign thewritten informed consent form.

Exclusion Criteria:

Patients meeting any one of the following criteria will be excluded from this study:

1. Previous treatment history:

2. Patients who received mitomycin and nitrosourea chemotherapy within 6 weeksbefore the first administration.

3. Patients who received the last systemic anti-tumor treatment, includingchemotherapy, radiotherapy, immunotherapy, biological agents or endocrinetherapy, etc., within 4 weeks before the first administration.

4. Patients who received hormonal anti-tumor treatment or small molecule targetedtherapy within 2 weeks before the first administration.

5. Patients who received local treatment such as radiotherapy for target lesionswithin 4 weeks before the first administration, and those who receivedpalliative local treatment for non-target lesions within 2 weeks before thefirst administration.

6. Patients who received non-specific immunomodulatory treatment (such asinterleukin, interferon, thymosin, tumor necrosis factor, etc., excluding IL-11used for treating thrombocytopenia) within 2 weeks before the firstadministration.

7. Patients who previously received the experimental drugs IMM2510 and/or IMM27M;those who could not tolerate treatment with anti-CTLA-4 or PD-1/L1 inhibitors (due to toxic and side effects); those who previously used drugs targetingthree targets, namely anti-PD-1/L1, VEGF, and CTLA-4 simultaneously in the sameregimen.

8. Patients who received traditional Chinese medicine with anti-tumor indicationswithin 1 week before the first administration.

9. Patients who participated in other clinical trials within 4 weeks before thefirst administration.

10. Those with a known severe allergic history to any component of the experimentaldrug, or those with a history of severe allergic reactions to chimeric or humanizedantibodies or fusion proteins.

11. Those who had any immune-related adverse events (irAE) of grade ≥ 3 in CTCAE V5.0 orthat led to the termination of immunotherapy during previous treatment with anyimmunotherapy drugs.

12. Those diagnosed with other malignant tumors within 5 years before enrollment.Exceptions: 1) Cervical carcinoma in situ and non-melanoma skin cancer that havebeen cured; 2) Patients who have been radically cured, unless the patients have beenin complete remission for at least 2 years before enrollment and do not requireother treatments or will not require other treatments during the study period.

13. Those with an active second primary cancer that is known and has had no recurrencewithin 5 years. Exceptions: 1) The investigator believes that both primary cancerscan benefit from this study; 2) The investigator has clearly excluded which primarytumor the metastatic lesions belong to.

14. Patients with primary central nervous system (CNS) malignant tumors or those withactive CNS metastases that failed local treatment (radiotherapy or surgicaltreatment). However, the following patients are allowed to enroll: a. Patients withasymptomatic brain metastases; b. Patients with clinically stable symptoms (i.e., noradiological progression was seen within 4 weeks before the first administration,and any neurological symptoms have returned to the baseline level), and who have notrequired corticosteroid hormones and other treatments for brain metastases for ≥ 4weeks.

15. Patients with hypertension that cannot be controlled by drugs (systolic bloodpressure remains > 140 mmHg or diastolic blood pressure > 90 mmHg after standardtreatment), or with pulmonary hypertension or unstable angina pectoris; those whohad a myocardial infarction or underwent bypass or stent surgery within 6 monthsbefore administration; those with a history of chronic heart failure of grade 3 - 4according to the New York Heart Association (NYHA) criteria; those with clinicallysignificant valvular diseases; those with severe arrhythmias requiring treatment (except atrial fibrillation and paroxysmal supraventricular tachycardia), includingQTcF ≥ 450 ms for men and ≥ 470 ms for women (calculated by the Fridericia formula);those with cerebrovascular accidents (CVA) or transient ischemic attacks (TIA),etc., within 12 months before enrollment.

16. Those with a history of arterial thrombosis, deep vein thrombosis or pulmonaryembolism within 3 months before administration.

17. Those with a history of moderate or severe dyspnea at rest due to advanced malignanttumors or their complications or severe primary lung diseases, or those currentlyrequiring continuous oxygen inhalation treatment, or those with a history ofinterstitial lung disease (ILD) or pneumonia, severe chronic obstructive pulmonarydisease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.

18. Those with diseases that may cause gastrointestinal bleeding or perforation (such asduodenal ulcer, intestinal obstruction, acute Crohn's disease, ulcerative colitis,extensive resection of the stomach and small intestine, etc.); patients with chronicCrohn's disease and ulcerative colitis (except those who have undergone totalcolectomy and rectal resection) should be excluded even during the inactive period;those with hereditary non-polyposis colorectal cancer or familial adenomatouspolyposis syndrome; those with a history of intestinal perforation or intestinalfistula that have not been cured after surgical treatment; esophageal and gastricvarices; or the presence of cancer thrombus in the main portal vein; those requiringrepeated drainage due to uncontrollable thoracic, abdominal or pericardial effusionthat requires puncture and drainage treatment or those with obvious symptoms.

19. Those with evidence of severe active infections that cannot be controlled (such assepsis, bacteremia, viremia, etc.).

20. Those with active tuberculosis infection.

21. Those with active hepatitis B (HBsAg positive, and HBV DNA higher than the lowerlimit of detection, and excluding hepatitis caused by drugs or other reasons), orthose with active hepatitis C (anti-HCV antibody positive, and HCV RNA higher thanthe lower limit of detection).

22. Those with a history of immunodeficiency, including human immunodeficiency virus (HIV) infection, or other immunodeficiency diseases, or those with a history oforgan transplantation or hematopoietic stem cell transplantation.

23. Those with a history of active autoimmune diseases, including but not limited tosystemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory boweldiseases, Hashimoto's thyroiditis, autoimmune thyroid diseases, multiple sclerosis,etc. Exceptions:

24. Hypothyroidism that can be controlled only by hormone replacement therapy.

25. Skin diseases that do not require systemic treatment (such as vitiligo,psoriasis).

26. Controlled celiac disease.

27. Those who are currently using immunosuppressants or systemic hormone therapy (prednisone at a dose of ≥ 10 mg/day or other equivalent hormones) and are stillusing them within 2 weeks before enrollment.

28. Those who underwent major surgery within 4 weeks before the first administration andhave not fully recovered, or those who plan to undergo major surgery within thefirst 12 weeks after receiving the study drug; those who received minor surgicaloperations 2 days before enrollment.

29. Those with incompletely healed skin wounds, surgical sites, trauma sites, severemucosal ulcers or fractures, and whom the investigator judges to be at risk ofbleeding if participating in this study.

30. Those who received anti-tumor vaccines or live vaccines within 4 weeks before thefirst administration, or those who plan to receive anti-tumor vaccines or livevaccines during the study period.

31. Those with a clear history of neurological or mental disorders in the past, such asepilepsy, dementia, and with poor compliance.

32. Patients with a history of alcoholism or drug abuse within the past year, or with ahistory of fainting during acupuncture or blood drawing, or those who cannottolerate venipuncture for blood collection.

33. Women who are pregnant or breastfeeding; those who do not agree to take sufficientcontraceptive measures together with their partners during the study period andwithin 6 months after the end of receiving the experimental drug.

34. The investigator believes that there are other reasons why the patient is notsuitable to participate in this trial.