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

NCT ID: NCT04739111

Last Updated: 2021-02-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-29
• Study Completion Date: 2024-02-29

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.

Conditions

Advanced Malignant Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Arms

All participants will receive treatment with LDP combined with CDP1. 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.

Group Type: EXPERIMENTAL

Human Anti-PD-L1 Monoclonal Antibody Injection (LDP) Combined with Recombinant Anti-EGFR Human Mouse Chimeric Monoclonal Antibody Injection (CDP1)

Intervention Type: DRUG

In the dose-escalation phase, CDP1 400 mg/ m2 will be given in the first week, then 250 mg/m2 will be given evert week. LDP will be given every two weeks with dose climbing of 5 mg/kg, 10 mg/kg, 20 mg/kg. Dose in the dose-expansion phase according to the assesment in the dose-escalation phase.

Interventions

Human Anti-PD-L1 Monoclonal Antibody Injection (LDP) Combined with Recombinant Anti-EGFR Human Mouse Chimeric Monoclonal Antibody Injection (CDP1)

In the dose-escalation phase, CDP1 400 mg/ m2 will be given in the first week, then 250 mg/m2 will be given evert week. LDP will be given every two weeks with dose climbing of 5 mg/kg, 10 mg/kg, 20 mg/kg. Dose in the dose-expansion phase according to the assesment in the dose-escalation phase.

Intervention Type: DRUG

Other Intervention Names

LDP combined with CDP1

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

West China Hospital

OTHER

Sponsor Role: collaborator

Dragonboat Biopharmaceutical Company Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yongsheng Wang

Role: STUDY_CHAIR

West China Hospital

Locations

Dragonboat Biopharmaceutical,Co.,Ltd

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wenli Ji

Role: CONTACT

wenli.ji@dragonboatbio.com

#86#021-50276381-637

Zhen Jin

Role: CONTACT

zhen.jin@dragonboatbio.com

#86#021-50276381

Facility Contacts

Wenli Ji

Role: primary

wenli.ji@dragonboatbio.com

#86#021-50276381-637

Zhen Jin

Role: backup

zhen.jin@dragonboatbio.com

#86#021-50276381

Other Identifiers

BCSW-LDP+CDP1-Ⅰ-01

Identifier Type: -

Identifier Source: org_study_id