Clinical trial NCT04718584: the Efficacy and Safety of LDP in Patients With Urinary and Male Genital Tumors
Official title: A Single-arm, Open, Multicenter, Phase II Clinical Study of the Efficacy and Safety of Human Anti-PD-L1 Monoclonal Antibody Injection (LDP) in the Treatment of Urinary and Male Genital Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Bladder Cancer
Renal Carcinoma
Advanced Penile Carcinoma
Lead sponsor: Dragonboat Biopharmaceutical Company Limited
Sponsor class: INDUSTRY
Collaborators: name: Fudan University
First posted: 2021-01-22
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm,open, multicenter, phase II clinical study of the efficacy and safety of human anti-PD-L1 monoclonal antibody Injection (LDP) in the treatment of urinary and male genital tumors.

Detailed description: This trial is a single arm, open, multicenter, Ⅱ period clinical research. Three cohorts were included, 127 subjects were enrolled (Cohort 1: about 60 subjects with surgically suitable muscular-invasive bladder cancer; Cohort 2: about 40 subjects with advanced Non-clear Cell Renal Carcinoma; Cohort 3: about 27 subjects with advanced penile carcinoma. After confirmation of inclusion, intravenous infusion of 10mg/kg human anti-PD-L1 monoclonal antibody injection (LDP) was given. The initial efficacy and safety of drugs in different tumor species in the cohort above will be observed.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 (inclusive), ≤18 (inclusive)
2. Patients with muscular-infiltrating bladder cancer suitable for surgery; advanced opaque cell renal carcinoma; advanced penile carcinoma
3. The estimated survival time is more than 3 months.
4. At least one assessable tumor lesion according to RECIST1.1 (in cohort 1, evaluate lesion is accept);
5. ECOG physical strength score 0-1;
6. Enough organ function: Blood routine (no blood transfusion or colony stimulating factor (G-CSF) treatment within 14 days):ANC≥1.5×109 / L, PLT≥75×109 / L, Hb≥80g/L; Liver function: TBIL≤1.5×ULN, ALT≤2.5×ULN, AST≤2.5×ULN (ALT,AST≤5×ULN for liver metastasis patients); Renal function: Cr ≤ 1.5 × ULN, and creatinine clearance \> 50 ml /min(according to Croft Gault formula) ; Coagulation function: APTT≤ 1.5 ×ULN, PT ≤ 1.5 × ULN, INR ≤ 1.5 × ULN;
7. Eligible patients (male and female) with fertility must agree to use reliable methods of contraception (hormone or barrier or abstinence) during the trial period and at least 6 months after the last dose; The blood or urine pregnancy test within 7 day before being selected must be negative for the female patients of childbearing age;
8. Subjects must give informed consent to this study before the study, and voluntarily sign a written informed consent;

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;
6. Immunorelated adverse events ≥ Grade 3 were observed in previous immunotherapy except for PD-1 or PD-L1 inhibitors;
7. Patients have any active autoimmune diseases or a history of autoimmune diseases (e.g., but not limited to: systemic lupus erythematosus, autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, vitiligo, etc.); Complete remission of asthma in childhood can be included if in adults without any intervention;Asthma patients requiring bronchodilators for medical intervention were excluded);
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, such as before the use of contrast agents;
9. Malignancies that were active within the last 2 years prior to initial administration (except for the tumors targeted in this study);
10. Uncontrolled active hepatitis B (HBsAg positive with HBV DNA copy number \> 103/ mL or HBV DNA titer \>200 IU/ mL); Hepatitis C;
11. Syphilis infection (syphilis antibody positive) and HIV positive patients.
12. 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;
13. Patients with a history of other serious systemic diseases who have been determined by the investigator to be unsuitable for participation in clinical trials;
14. Known alcohol or drug dependence;
15. Mental disorder or poor compliance;
16. Women who are pregnant or lactating;
17. Have received live attenuated vaccine within 4 weeks before the first administration or scheduled to receive during the study period.
18. The Investigator considers that the subject is unsuitable to participate in this study because of any clinical or laboratory test abnormalities or other reasons.

Primary outcomes:
measure: Case complete response （pCR）
timeFrame: At the end of the cycle 3 of treatment (each cycle is 14 days).
measure: Objective response rate (ORR)
timeFrame: From first dose of LDP through 21 days after last dose of LDP up to 2 years.
Secondary outcomes:
measure: Recurrence-free survival (RFS)
timeFrame: One year after surgery or disease progression or intolerant toxicity, up to 2 years.
measure: Progression-free survival （PFS）
timeFrame: From first dose of LDP, up to 2 years.
measure: Disease control rate (DCR)
timeFrame: From first dose of LDP, up to 2 years.
measure: Duration of response (DOR)
timeFrame: From first dose of LDP, up to 2 years.
measure: Overall survival (OS)
timeFrame: From first dose of LDP, up to 2 years.
measure: Incidence of adverse events
timeFrame: From first dose of LDP through 30 days after last dose of LDP, up to 5 months.
measure: Incidence of abnormal vital signs
timeFrame: From first dose of LDP through 30 days after last dose of LDP, up to 5 months.
measure: Incidence of abnormal ECOG scores
timeFrame: From first dose of LDP through 30 days after last dose of LDP, up to 5 months.
measure: Incidence of abnormal laboratory tests results
timeFrame: From first dose of LDP through 30 days after last dose of LDP, up to 5 months.
measure: Incidence of abnormal physical examinations
timeFrame: From first dose of LDP through 30 days after last dose of LDP, up to 5 months.
measure: anti-drug antibody (ADA)
timeFrame: In Cohort 1: before administration ,before surgery; In Cohort 2, 3: before administration, up to 4 months.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Dragonboat Biopharmaceutical,Co.,Ltd
state: Shanghai
Study officials:
affiliation: Fudan University
name: Dingwei Ye
role: STUDY_CHAIR
References: