A Clinical Trial to Evaluate Effect of IAP0971 in Patients With Advanced Malignant Tumors

Inclusion Criteria:

1. Age of 18-75 years old (including cut-off value), regardless of gender.

2. Phase I only: patients with histologically confirmed advanced or metastaticmalignant solid tumors who have failed to respond to standard treatment, who have nostandard treatment options, who are not currently applicable to standard treatment,or who have been assessed by the investigator to benefit from this treatment.

3. Phase II only: patients with histologically confirmed locally advanced (stage IIIBor IIIC) or metastatic (stage IV) non-small cell lung cancer (NSCLC) that is notamenable to complete surgical resection and definitive concurrent chemoradiotherapy.Note: For patients with locally advanced stage (stage IIIB/IIIC) who cannot acceptradical concurrent/sequential chemoradiotherapy, they need to be evaluated byrelevant professional physicians and confirmed by written records.

4. Phase II only: no prior systemic antitumor therapy for locally advanced ormetastatic NSCLC (except for patients who received adjuvant/neoadjuvant chemotherapyor definitive concurrent or sequential chemoradiotherapy for locally advanceddisease and disease progression ≥6 months after the last treatment).

5. Phase II only: PD-L1 positive (TPS≥50%) as determined by IHC, and patients werenegative for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) by immunohistochemistry.

6. have at least one measurable lesion according to RECIST 1.1 criteria (tumor lesionlocated in the previous radiotherapy area or other locoregional treatment site,generally not considered a measurable lesion unless the lesion has clearlyprogressed or persists beyond three months of radiotherapy).

7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

8. predicted survival time ≥3 months.

9. with adequate organ function:

① Blood system (no blood transfusion or hematopoietic stimulation therapy within 14days) : absolute neutrophil count (ANC) ≥1.5×109/L, platelet count (PLT) ≥100×109/L,hemoglobin (HGB) ≥90 g/L; ② Liver function: total bilirubin (TBIL) ≤1.5 times theupper limit of normal value (ULN), except Gilbert's syndrome Out of; Aspartateaminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 times ULN, andpatients with liver metastasis or liver cancer need AST and ALT≤5.0 times ULN andtotal bilirubin ≤3.0 times ULN;

② Renal function: serum creatinine (Cr) ≤1.5 times ULN; If creatinine > 1.5 timesULN, creatinine clearance (Ccr) ≥50 mL/min (calculated by Cockcroft-Gault formula)was required.

③ Coagulation function: prothrombin international normalized ratio (INR) ≤1.5 timesULN, activated partial thromboplastin time (APTT) ≤1.5 times ULN, patients withliver metastasis or liver cancer need INR and APTT≤2.5 times ULN.

10. Eligible patients (men and women) of childbearing potential must consent to use areliable method of contraception (hormonal or barrier methods or abstinence) withtheir partner during the trial and for at least 6 months after the last dose; Femalepatients of reproductive age had to have a negative blood pregnancy test within 7days before the first use of the study drug.

11. Subjects must give informed consent for this study and voluntarily provide writteninformed consent before the trial.

Exclusion Criteria:

1. Phase II only: small cell lung cancer or sarcomatoid lesion confirmed byhistopathology.

2. Phase II only: previous immunotherapy, including immune checkpoint inhibitors (e.g.,anti-PD-1 /PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (e.g. ICOS, CD40, CD137, GITR, OX40 antibody, etc.), immune cell therapy, and anytreatment targeting the mechanism of tumor immune action.

3. Phase I only: patients received anti-tumor therapy such as systemic chemotherapy,radiotherapy, biological therapy, endocrine therapy, or immunotherapy within 4 weeksbefore the first dose of study drug; The following drugs were excluded according tothe following criteria:

① Treatment with a small-molecule tyrosine kinase inhibitor within 2 weeks beforethe first dose;

② Palliative local treatment for non-target lesions within 2 weeks before the firstdose; Patients received non-specific immunomodulatory therapy (such as interleukin,interferon, thymosin, not including IL-11) within 2 weeks before the first dose;

③ received Chinese herbal medicine or Chinese patent medicine with anti-tumorindications within 2 weeks before the first dose.

4. received other investigational drugs or treatments within 4 weeks before the studydrug.

5. received systemic glucocorticoids (prednisone > 10 mg/ day or equivalent) or otherimmunosuppressive agents within 14 days before the first dose of study drug; The useof topical, ocular, intra-articular, nasal, and inhaled glucocorticoids wasexcluded. Short-term prophylaxis with glucocorticoids (e.g., to prevent contrastallergy).

6. the adverse effects of previous antineoplastic therapy have not recovered to CTCAE 5.0 grade ≤1 or the relevant requirements of the inclusion criteria (except fortoxicities without safety risks judged by the investigators, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacementtherapy).

7. major surgical procedures (excluding needle biopsies) within 4 weeks before thefirst dose of study drug, major trauma, or the need for elective surgery during thetrial.

8. prior allogeneic hematopoietic stem-cell transplantation or organ transplantation.

9. clinically symptomatic parenchymal or meningeal metastases.

10. have active infection and currently require intravenous anti-infective therapy.

11. have a history of immunodeficiency, including testing positive for humanimmunodeficiency virus (HIV) antibodies.

12. active hepatitis B (HBsAg positive and HBV-DNA positive or greater than the upperlimit of normal), active hepatitis C (hepatitis C virus antibody positive and HCVRNA positive or greater than the upper limit of normal).

13. received any live vaccine within 4 weeks before the first dose of study drug.

14. known hypersensitivity to any antibody-based drug (NCI CTCAE grade 5.0 ≥3) or to thestudy drug, active ingredient, or inactive excipients of a PD-1/PD-L1 inhibitor.

15. with severe and uncontrollable lung diseases (severe infectious pneumonia,interstitial lung disease, etc.); Or other moderate-to-severe lung diseases thatseverely affect respiratory function that may interfere with the detection ormanagement of drug-related pulmonary toxicity.

16. have a history of severe cardiovascular and cerebrovascular disease, including butnot limited to:

① Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmiarequiring clinical intervention, II-III degree atrioventricular block, etc.

② Mean QT interval corrected with Fridericia's method (QTcF) > 470 ms;

③ Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, orother grade 3 or above cardiovascular and cerebrovascular events occurred within 6months before the first dose; ④ patients with New York Heart Association (NYHA)functional class ≥II heart failure or left ventricular ejection fraction (LVEF) < 50% or structural heart disease with high risk as judged by other investigators; And 5) clinically uncontrolled hypertension.

17. have an active or previous autoimmune disease (e.g., systemic lupus erythematosus,rheumatoid arthritis, vasculitis, etc.) with the possibility of recurrence, exceptclinically stable autoimmune thyroid disease, type I diabetes mellitus, vitiligo,cured atopic dermatitis in children, and psoriasis (within the past 2 years) thatdoes not require systemic treatment."

18. had other malignancies within 5 years before study administration, except formalignancies that could be expected to be cured with treatment (including, but notlimited to, adequately treated thyroid cancer, carcinoma in situ of the cervix,basal or squamous cell skin cancer, or ductal carcinoma in situ of the breasttreated with radical surgery).

19. have clinically uncontrollable effusion in the third space, which was judged by theinvestigator to be not suitable for enrollment.

20. known alcohol or drug dependence.

21. with mental disorders or poor adherence.

22. pregnant or lactating women.

23. The participant was deemed by the investigator to have a history of other serioussystemic diseases or to be ineligible for the study for other reasons.