A Study to Evaluate the Safety and Efficacy of HB0025 Injection in Patients With Advanced Solid Tumor

Inclusion Criteria:

1. Male or female, age between 18-75 years old (include 18- and 75-year-old);

2. Be able to fully understand and voluntarily sign the informed consent form, and bewilling and able to comply with the clinical research and follow-up visitprocedures；

3. Dose escalation phase 3.1 Non-small cell lung cancer and meet all followingconditions； 3.1.1 Non-small cell lung cancer (NSCLC) confirmed by histology orcytology; 3.1.2 Not suitable for surgical resection, recurrence, metastasis, orlocally advanced stage; 3.1.3 Patients with tyrosine kinase inhibitor (TKI) drugsensitivity mutations of epidermal growth factor receptor (EGFR) and anaplasticlymphoma kinase (ALK) translocation, who have experienced disease progression afterstandard treatment with TKI targeted drugs, or are intolerant to standard treatmentwith TKI targeted drugs; 3.1.4 No known ROS proto-oncogene 1 (ROS1), neurogenictyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations or otheroncogenic driver gene mutations, and there are approved therapeutic drugs for theabove gene mutations (there are therapeutic drugs for genomic changes).

3.2 Endometrial cancer and meet all following conditions 3.2.1 Endometrial cancerconfirmed by histology or cytology, the pathological types include but are notlimited to endometrioid carcinoma, serous carcinoma, clear cell carcinoma,undifferentiated carcinoma, dedifferentiated carcinoma, mixed carcinoma, andcarcinosarcoma; 3.2.2 Not suitable for surgical resection, recurrence, metastasis,locally advanced stage; 3.2.3 No previous systemic anti-tumor treatment (excludingadjuvant therapy and neoadjuvant therapy);

4. Dose expansion phase 4.1 Non-small cell lung cancer and meet all followingconditions 4.1.1 Non-squamous non-small cell lung cancer (Nonsq-NSCLC) or squamousnon-small cell lung cancer (Sq-NSCLC) confirmed by histology or cytology (forcentral squamous cell carcinoma, the investigator and the sponsor jointly decidewhether to enroll based on the risk of bleeding and the benefit-risk ratio of thesubject); 4.1.2 Not suitable for surgical resection, recurrent, metastatic, locallyadvanced; Negative for TKI drug sensitivity mutations of epidermal growth factorreceptor (EGFR), anaplastic lymphoma kinase (ALK) translocation; 4.1.3 Negative forTKI drug sensitivity mutations of epidermal growth factor receptor (EGFR),anaplastic lymphoma kinase (ALK) translocation; 4.1.4 No known ROS proto-oncogene 1 (ROS1), neurogenic tyrosine receptor kinase (NTRK)，proto-oncogene B-raf (BRAF), RETmutations or other oncogenic driver gene mutations, for which there are approvedtherapeutic drugs for the above gene mutations (there are therapeutic drugs forgenomic changes); 4.1.5 No previous systemic anti-tumor treatment (for subjects whohave received adjuvant/neoadjuvant treatment for non-metastatic disease with thepurpose of cure, if disease progression occurs within 6 months of the end of thelast treatment, the treatment regimen is considered as one systemic treatment and isnot allowed to be included).

4.2 Endometrial cancer and meet all following conditions 4.2.1 Endometrial cancerconfirmed by histology or cytology, with pathological types including but notlimited to endometrioid carcinoma, serous carcinoma, clear cell carcinoma,undifferentiated carcinoma, dedifferentiated carcinoma, mixed carcinoma, andcarcinosarcoma; 4.2.2 Not suitable for surgical resection, recurrence, metastasis,locally advanced stage; 4.2.3 No previous systemic anti-tumor treatment (forsubjects who have received adjuvant/ neoadjuvant treatment for non-metastaticdisease with the purpose of cure, if disease progression occurs within 6 months ofthe end of the last treatment, the treatment regimen is considered as 1 systemictreatment and is not allowed to be included in the group);

5. Patients who have not received anti-tumor treatment or other clinical trial drugswithin 4 weeks before the first administration of HB0025 (for small moleculetargeted drugs, this is within 2 weeks before the first use of the study drug orwithin 5 half-lives of the drug (whichever is longer); have completed systemicpalliative radiotherapy for at least 4 weeks or local palliative radiotherapy for atleast 2 weeks (in the baseline tumor assessment, the target lesions defined can beexcluded if they are not in the local radiotherapy area); have not systematicallyused (for 2 consecutive weeks) traditional Chinese medicine with anti-tumorindications within 2 weeks before the first use of the study drug;

6. There is at least one measurable tumor lesion (according to RECIST 1.1 standard);Note: Lesions that have been previously treated with local therapy (e.g.,radiofrequency ablation, anhydrous ethanol or acetic acid injection, cryoablation,high-intensity focused ultrasound, trans-arterial chemoembolization, localradiotherapy, etc.) are not considered measurable lesions unless there is clearprogression.

7. ECOG score of 0 or 1;

8. The expected survival period is not less than 12 weeks;

9. The following laboratory indicators must be met:

9.1 Absolute neutrophil count ≥1.5×10⁹/L; 9.2 Platelet count ≥90×10⁹/L; 9.3Hemoglobin ≥90 g/L; Note: The above three requirements require that the patient hasnot received any blood component or cell growth factor support therapy within twoweeks before blood collection.

9.4 Creatinine clearance ≥50 mL/min (Cockcroft-Gault Formula); 9.5 Total bilirubin ≤1.5×ULN; 9.6 Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5× ULN; If the investigator determines that the increase is due to livermetastasis of the tumor, ALT和AST≤5×ULN; 9.7 Prothrombin time (PT)≤1.5×ULN, partialthromboplastin time (APTT)≤1.5×ULN; 9.8 Urine dipstick test results show protein inurine<1+; if urine protein ≥1+, 24-hour urine protein content<1 g.

10. The toxicity from previous treatment has recovered to grade 1 (except for toxicitysuch as alopecia that the investigator determines does not pose a safety risk);

11. Females and males of childbearing age must agree to take effective contraceptivemeasures during the study and within 3 months after the last dose of HB0025 aftersigning the informed consent form. Female subjects of childbearing age must have anegative pregnancy test result during the screening period.

Exclusion Criteria:

1. Brain metastasis with central nervous system symptoms; for subjects withasymptomatic brain metastasis: after receiving relevant treatment, imaging andneurological examinations are in a stable state for more than 4 weeks. If there isno imaging evaluation, the neurological examination is in a stable state for morethan 4 weeks under glucocorticoid treatment, and the treatment dose for at least 2weeks is ≤10mg/day of prednisone or other hormones of the same dose, they can beincluded in the group;

2. Active autoimmune diseases or a history of autoimmune diseases requiring systemictreatment within 2 years before screening, including hypothyroidism, Graves'ophthalmo-pathy, Hashimoto's thyroiditis or type 1 diabetes, but childhood asthma orallergic asthma that did not occur within 2 years before screening can be excluded;

3. Patients who received >10 mg/day of prednisone or equivalent dose of systemicglucocorticoids or other immunosuppressants within 2 weeks before screening, or whoreceived topical, intraocular, intraarticular, intranasal or inhaled hormones forprevention (such as contrast agent allergy) or treatment of non-autoimmune diseases (such as delayed hypersensitivity reactions caused by contact allergens) wereallowed to be included in the group;

4. Any of the following infections:

4.1 Active infection within 2 weeks prior to screening, requiring antibiotictreatment for >7 days; 4.2 Active pulmonary tuberculosis (based on history); 4.3 HIVpositive; 4.4 Active hepatitis B or hepatitis C. Asymptomatic hepatitis B viruscarriers (HBV DNA titer below the detection limit) or clinically cured hepatitis C (HCV RNA test negative) are allowed to enroll;

5. Patients who have received immune checkpoint inhibitors (ICI) combined withanti-vascular therapy, such as anti-PD-(L)-1 antibody combined with anti-VEGF, VEGFRantibody, or TKI drugs with anti-vascular effects such as anlotinib;

6. Patients with a history of severe allergies, previous grade 3-4 immune-relatedadverse events (irAEs) or treatment discontinuation (except for grade 3 endocrineabnormalities that can be controlled by hormone replacement therapy); patients withgrade 3-4 allergic reactions when receiving other monoclonal antibody treatments, orpatients with known allergies to protein drugs or recombinant proteins, HB0025 drugcomponents, and chemotherapy drug components;

7. Uncontrolled arterial hypertension (systolic blood pressure ≥ 150 mmHg or diastolicblood pressure ≥ 100 mmHg) despite standard treatment;

8. Suffering from the following serious comorbidities:

8.1 Subjects with a history of arterial thrombosis or deep vein thrombosis within 6months before screening, or subjects with evidence or history of bleeding tendencywithin 2 months before enrollment, regardless of severity (For the EC cohort: thedecision on whether to enroll subjects with evidence or history of bleeding tendencywithin 2 months before enrollment was made by the investigator and the sponsor); 8.2Previous or current bleeding or coagulation disorders; 8.3 Past history ofmyocarditis, cardiomyopathy, or malignant arrhythmias. Clinically significant (e.g.,active) cardiovascular and cerebrovascular diseases within 6 months prior toscreening, including but not limited to unstable angina requiring hospitalization,myocardial infarction, New York Heart Association-classified congestive heartfailure ≥ II, severe arrhythmias that cannot be controlled by drugs, transientischemic attack (TIA), cerebrovascular accident (CVA) or vascular disease (e.g.,aortic aneurysm with risk of rupture), or other cardiac damage that may affect thesafety evaluation of the study drug (e.g., poorly controlled arrhythmias, myocardialischemia), etc.; 8.4 Gastrointestinal disorders or conditions that may causegastrointestinal bleeding or perforation (history of intestinal obstruction, acuteCrohn's disease, ulcerative colitis, esophageal varices, unhealed ulcers, unhealedwounds, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6months prior to screening). Subjects with chronic Crohn's disease and ulcerativecolitis (except those with total colon and rectal resection), even in the inactivestage, should be excluded; 8.5 Those who have had digestive tract perforation orfistula, urogenital system fistula, and have not recovered after surgical treatment; 8.6 Current clinically significant hydronephrosis that has not been relieved bynephrostomy or ureteral stenting; 8.7 Patients with third space effusion (such aspleural effusion, pericardial effusion or ascites) that is currently clinicallypoorly controlled and requires repeated puncture drainage or other local treatment; 8.8 Imaging (CT or MRI) shows that the tumor has invaded or surrounded importantblood vessels (lung cancer cohort only) or the investigators judge that the tumor isvery likely to invade important blood vessels and cause fatal bleeding during thefollow-up study; 8.9 Acute exacerbation of COPD within 1 month before first dose;

9. Patients who have used or are currently taking anticoagulants such as warfarin,heparin (except for tube sealing and deep vein catheterization), dabigatranetexilate, rivaroxaban, etc. within 7 days before the first study treatment; orpatients who have received aspirin, clopidogrel, dipyridamole, cilostazol, or otherdrugs known to inhibit platelet aggregation;

10. Received major surgical treatment, open biopsy or significant trauma within 4 weeksbefore drug administration; or required major elective surgical treatment during thestudy period. Received local invasive procedures (such as needles) within 1 weekbefore drug administration. Core biopsy), except for placement of a vascular accessdevice;

11. Those with past and/or current interstitial lung disease, pneumoconiosis,drug-related pneumonia, severe lung function impairment, etc. that may interferewith the detection and treatment of suspected drug-related pulmonary toxicity;

12. Pregnant or breastfeeding women;

13. History of allogeneic organ transplantation or hematopoietic stem celltransplantation;

14. Second tumor within 5 years before screening, excluding cured cervical cancer insitu, localized skin squamous cell carcinoma, basal cell carcinoma, breast ductalcarcinoma in situ or T1 urothelial carcinoma;

15. Received live virus vaccine within 30 days before screening;

16. During the screening period, patients with advanced Nonsq-NSCLC who are intolerantto the chemotherapy regimen of pemetrexed combined with carboplatin;

17. During the screening period, patients with advanced sq-NSCLC or EC who areintolerant to paclitaxel combined with carboplatin chemotherapy;

18. Subjects who are assessed by the investigator to be unsuitable for participating inthe trial due to other reasons.