Clinical trial NCT04739111: An Exploratory Clinical Study of LDP Combined With CDP1 in Patients With Advanced Malignant Tumor
Official title: An Exploratory Clinical Study of Human Anti-PD-L1 Monoclonal Antibody Injection (LDP) Combined With Recombinant Anti-EGFR Human Mouse Chimeric Monoclonal Antibody Injection (CDP1) in Patients With Advanced Malignant Tumor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Malignant Tumor
Lead sponsor: Dragonboat Biopharmaceutical Company Limited
Sponsor class: INDUSTRY
Collaborators: name: West China Hospital
First posted: 2021-02-04
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an exploratory clinical study of Human Anti-PD-L1 Monoclonal Antibody Injection (LDP) combined with Recombinant Anti-EGFR Human Mouse Chimeric Monoclonal Antibody Injection (CDP1) in patients with advanced malignant tumor.

Detailed description: This is an open, dose-escalation and dose-extension exploratory clinical study for patients with advanced malignancy who have failed standard therapy. In the dose-escalation phase, a fixed dose of CDP1 will be given once a week, while LDP will be given every two weeks with dose climbing. Then, cohort studies (cohorts 1 to 5) will be conducted during the dose-expansion phase. The purpose is to preliminarily evaluate the safety and efficacy of LDP combined with CDP1 in the treatment of patients with advanced malignant tumor, and to determine the recommended dose for clinical trial.

Eligibility criteria: 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, evaluate lesion is accept);
* 4. ECOG physical strength score 0-2;
* 5. No serious abnormal blood system, liver function, kidney function or coagulation function: 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 Croft Gault 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 7 days before the first dose.Male subjects and female subjects of reproductive age must use adequate contraception and have no plans to donate sperm or eggs within 3 months from the date of signing informed consent for the study to the date of the last study drug treatment.
* 7. Subjects must give informed consent to this study before the study, and voluntarily sign a written informed consent;
* 8.Locally advanced or metastatic malignancies diagnosed by histopathology, which have failed standard treatment, have no standard treatment regimen, or are not suitable for standard treatment at this stage. In the dose-expansion phase: cohort 1: head and neck squamous cell carcinoma;Cohort 2: colorectal cancer, RAS genotype was wild type;Cohort 3: esophageal squamous cell carcinoma;Cohort 4: Penile cancer;Cohort 5: Female reproductive system tumors (endometrial, cervical, ovarian).

Exclusion Criteria:

* 1. Received radiotherapy, chemotherapy, targeted therapy, endocrine therapy or immunotherapy within 4 weeks before the first administration, or other unlisted clinical trial drug therapy (mitomycin and nitrosourea are 6 weeks from the last administration, oral fluorouracil drugs such as tegiol and capecitabine are at least 2 weeks from the last administration, small molecule targeted drugs are at least 2 weeks or at least interval 5 half-life (Subject to the longer time) from the last administration, and traditional Chinese medicine with antitumor indications are at least 2 weeks from the last administration.
* 2. Major organ surgery (excluding puncture biopsy) or significant trauma occurred within 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 cord metastases are not suitable for inclusion as judged by the investigator
* 5. Patients who had previously received PD-1 or PD-L1 inhibitors or anti-EGFR monoclonal 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 lupus erythematosus, rheumatoid arthritis, vasculitis, interstitial lung disease, etc.);
* 8. Patients who received systemic corticosteroid (prednisone \> 10mg/ day or equivalent) or other immunosuppressive therapy within 14 days prior to initial dosing; Exceptions include: topical, ocular, intraarticular, intranasal, and inhaled corticosteroids;Short-term use of corticosteroids for preventive treatment;
* 9. Uncontrolled active hepatitis B (HBsAg positive with HBV DNA copy number \> 103/ mL or HBV DNA titer \>200 IU/ mL); Hepatitis C;Syphilis infection (syphilis antibody positive) and HIV positive patients.
* 10. A history of serious cardiovascular disease, including ventricular arrhythmias requiring clinical intervention;Acute coronary syndrome, congestive heart failure, stroke, or other grade 3 or higher cardiovascular events within 6 months;New York Heart Association (NYHA) cardiac function grade ≥II or left ventricular ejection fraction (LVEF) \< 50%;Patients with clinically uncontrolled hypertension who are not suitable 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 first administration or scheduled to receive during the study period.
* 15. The Investigator considers that the subject is unsuitable to participate in this study 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 in this study, cured stage Ib cervical cancer or lower, non-invasive basal cell or squamous cell skin cancer, malignant melanoma with complete response (CR) \> for 10 years, and other malignant tumors with complete response (CR) BBB\>r 5 years)

Primary outcomes:
measure: Incidence of adverse events
timeFrame: From first dose of LDP combined of CDP1 through 30 days after last dose, up to 5 months.
measure: Dose Limiting Toxicities (DLT)
timeFrame: Time Frame: 28 days after first dose of LDP combined of CDP1, up to 24 months.
measure: Recommended dose for clinical trials
timeFrame: up to 24 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: From first dose of LDP combined of CDP1, up to 2 years.
measure: Duration of response (DOR)
timeFrame: From first dose of LDP combined of CDP1, an average of 6 months.
measure: Disease control rate (DCR)
timeFrame: From first dose of LDP combined of CDP1, up to 2 years.
measure: Progression-free survival (PFS)
timeFrame: From first dose of LDP combined of CDP1, an average of 6 months.
measure: Maximum plasma concentrations (Cmax)
timeFrame: an average of 6 months
measure: Area under the plasma concentration-time curve from zero to last concentration time (AUC0-t)
timeFrame: an average of 6 months
measure: Half-life (t1/2)
timeFrame: an average of 6 months
measure: anti-drug antibody (ADA)
timeFrame: an average of 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Dragonboat Biopharmaceutical,Co.,Ltd
state: Shanghai
Study officials:
affiliation: West China Hospital
name: Yongsheng Wang
role: STUDY_CHAIR
References: