An Exploratory Clinical Study of LDP Combined With CDP1 in Patients With Advanced Malignant Tumor

Inclusion Criteria:

• 1. Age ≥ 18 (inclusive), no gender limitation;
• 2. The estimated survival time is more than 3 months.
• 3. At least one assessable tumor lesion according to RECIST1.1 (in cohort 1, evaluatelesion is accept);
• 4. ECOG physical strength score 0-2;
• 5. No serious abnormal blood system, liver function, kidney function or coagulationfunction: ANC≥1.5×109 / L, PLT≥75×109 / L, Hb≥9g/dL; TBIL≤1.5×ULN, ALT≤2.5×ULN,AST≤2.5×ULN; Cr ≤ 1.5 × ULN, and creatinine clearance ≥ 50 ml /min(according to CroftGault formula),Urinary protein ≤2+;or 24-hour urinary protein ≤1g; APTT≤ 1.5 ×ULN, PT ≤ 1.5 × ULN, INR ≤ 1.5 × ULN;"
• 6.Blood or urine pregnancy tests are negative in women of childbearing age within 7days before the first dose.Male subjects and female subjects of reproductive age mustuse adequate contraception and have no plans to donate sperm or eggs within 3 monthsfrom the date of signing informed consent for the study to the date of the last studydrug treatment.
• 7. Subjects must give informed consent to this study before the study, and voluntarilysign a written informed consent;
• 8.Locally advanced or metastatic malignancies diagnosed by histopathology, which havefailed standard treatment, have no standard treatment regimen, or are not suitable forstandard treatment at this stage. In the dose-expansion phase: cohort 1: head and necksquamous cell carcinoma;Cohort 2: colorectal cancer, RAS genotype was wild type;Cohort 3: esophageal squamous cell carcinoma;Cohort 4: Penile cancer;Cohort 5: Femalereproductive system tumors (endometrial, cervical, ovarian).

Exclusion Criteria:

• 1. Received radiotherapy, chemotherapy, targeted therapy, endocrine therapy orimmunotherapy within 4 weeks before the first administration, or other unlistedclinical trial drug therapy (mitomycin and nitrosourea are 6 weeks from the lastadministration, oral fluorouracil drugs such as tegiol and capecitabine are at least 2weeks from the last administration, small molecule targeted drugs are at least 2 weeksor at least interval 5 half-life (Subject to the longer time) from the lastadministration, and traditional Chinese medicine with antitumor indications are atleast 2 weeks from the last administration.
• 2. Major organ surgery (excluding puncture biopsy) or significant trauma occurredwithin 4 weeks prior to the first administration.
• 3. The adverse effects of previous antitumor therapy have not recovered to CTCAE 5.0 ≤grade1 (except for alopecia)
• 4. Patients with clinical symptoms of brain metastases, spinal cord compression,cancerous meningitis, or other evidence of uncontrolled brain or spinal cordmetastases are not suitable for inclusion as judged by the investigator
• 5. Patients who had previously received PD-1 or PD-L1 inhibitors or anti-EGFRmonoclonal antibody or other immune checkpoint inhibitors and failed;
• 6. Immunorelated adverse events ≥ Grade 3 were observed in previous immunotherapy;
• 7. Patients with active or previous autoimmune diseases (such as systemic lupuserythematosus, rheumatoid arthritis, vasculitis, interstitial lung disease, etc.);
• 8. Patients who received systemic corticosteroid (prednisone > 10mg/ day orequivalent) or other immunosuppressive therapy within 14 days prior to initial dosing;Exceptions include: topical, ocular, intraarticular, intranasal, and inhaledcorticosteroids;Short-term use of corticosteroids for preventive treatment;
• 9. Uncontrolled active hepatitis B (HBsAg positive with HBV DNA copy number > 103/ mLor HBV DNA titer >200 IU/ mL); Hepatitis C;Syphilis infection (syphilis antibodypositive) and HIV positive patients.
• 10. A history of serious cardiovascular disease, including ventricular arrhythmiasrequiring clinical intervention;Acute coronary syndrome, congestive heart failure,stroke, or other grade 3 or higher cardiovascular events within 6 months;New YorkHeart Association (NYHA) cardiac function grade ≥II or left ventricular ejectionfraction (LVEF) < 50%;Patients with clinically uncontrolled hypertension who are notsuitable for the trial as determined by the investigator;
• 11. Known alcohol or drug dependence;
• 12. Mental disorder or poor compliance;
• 13. Women who are pregnant or lactating;
• 14. Have received live attenuated vaccine within 4 weeks before the firstadministration or scheduled to receive during the study period.
• 15. The Investigator considers that the subject is unsuitable to participate in thisstudy because of any clinical or laboratory test abnormalities or other reasons.
• 16.A malignant tumor that has been active in the past two years (Except for tumors inthis study, cured stage Ib cervical cancer or lower, non-invasive basal cell orsquamous cell skin cancer, malignant melanoma with complete response (CR) > for 10years, and other malignant tumors with complete response (CR) BBB>r 5 years)