Phase I Clinical Trial of Human Anti-PD-L1 Antibody Injection (LDP) in Patients With Advanced Malignant Tumors

NCT03908814 | Completed Phase 1

• 1 other identifier: LDP100001
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, open-label, multiple-dose, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of LDP in subjects with advanced malignant tumors.

Conditions

Advanced Tumors

Outcome Measures

Primary Outcomes (2)

• Number of participants with dose limiting toxicity (DLT)

  An DLT is defined as a ≥Grade 3 drug-related adverse event occurring within the first cycle (28 days) of dosing (excluding tumor flare causing local pain at sites of known or suspected tumor, localized rash, or a transient ≤Grade 3 infusion reaction) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

  At the end of Cycle 1 (28 days).

• Maximum tolerable dose (MTD)

  MTD refers to the highest dose which can satisfy the first cycle of the same dose group and the proportion of DLT occurring is less than 1/3 in the incremental dose stage. The dose of MTD required confirmation by 6 subjects.

  At the end of Cycle 1 (28 days).

Secondary Outcomes (8)

• Pharmacokinetic parameters: Observed Maximum Serum Concentration (Cmax) of LDP After Infusion

  Up to 22 Days

• Pharmacokinetic Parameters: Area Under the Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Infusion AUC(0-t) for LDP

  Up to 22 Days

• Pharmacokinetic parameters: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-00) After Infusion Pharmacokinetic parameters: AUC(0-00) for LDP

  Up to 22 Days

• Pharmacokinetic parameters: Apparent Terminal Half-life (t1/2) of LDP After Infusion

  Up to 22 Days

• Immunogenicity indicators: Number of participants with positive anti-drug antibodies (ADA)

  Up to 176 Days

Study Arms (1)

Drug: LDP

EXPERIMENTAL

This is a dose-escalation trial, all participants will receive treatment with LDP. Participants enrolled in this trial may receive one of the following doses dependent upon time of enrolment into the study. Cohort 1: 0.1 mg/kg Cohort 2: 0.3 mg/kg Cohort 3: 1 mg/kg Cohort 4: 3 mg/kg Cohort 5: 10 mg/kg Cohort 6: 10 mg/kg

Drug: Whole Human Anti-PD-L1 Antibody Injection (LDP)

Interventions

Whole Human Anti-PD-L1 Antibody Injection (LDP) DRUG

Dose escalation study evaluating six dose levels (0.1, 0.3, 1, 3 , 10and 20 mg/kg) of LDP.

Also known as: LDP

Drug: LDP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 (inclusive), regardless of gender
• Histologically or cytologically confirmed patients with advanced malignant tumors who fail to receive standard treatment or have no standard treatment or are not suitable for standard treatment at this stage;
• The estimated survival time is more than 3 months.
• At least one assessable tumor lesion (solid tumors according to RECIST 1.1, lymphoma according to Lugano 2014);
• ECOG physical strength score 0-1;
• 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=5×ULN for liver metastasis patients, AST≤5×ULN);Renal function: Cr ≤ 1.5 × ULN, and creatinine clearance \> 50 ml (according to Croft - Gault formula) Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5 times ULN, prothrombin time (PT) ≤ 1.5 times ULN, international normalized ratio (INR) ≤ 1.5 times ULN;
• 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; female patients of childbearing age are selected before the election. The blood or urine pregnancy test within the day must be negative;
• Prior to the trial, the subject shall have informed consent to the study and voluntarily sign a written form of informed consent;

You may not qualify if:

• 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 at least 6 weeks from the last administration, oral fluorouracil drugs such as tegiol and capecitabine are at least 2 weeks from the last administration, and small molecule targeted drugs are at the last administration). At least 2 weeks, or at least 5 half-lives, whichever is longer；
• Major organ surgery (excluding puncture biopsy) or significant trauma occurred within 4 weeks before the first administration.
• Adverse reactions of antineoplastic therapy in the past have not been restored to CTCAE grade 5.0≤1 (except for hair loss and other adverse reactions that the investigator judges have no safety risk).
• Brain metastasis, spinal cord compression, cancerous meningitis with clinical symptoms, or other evidence that the metastasis of brain and spinal cord has not yet been controlled, are not suitable for the group judged by the researchers; patients with suspected clinical symptoms of brain or pia mater diseases need to be excluded by CT/MRI examination;
• Those who have previously received treatment with PD-1 or PD-L1 inhibitors;
• In the past, immune-related adverse events (\> grade 3) have occurred in immunotherapy (irAE, see Appendix 5)；
• Patients with active or recurrent autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.)；
• Current or previous patients with interstitial lung disease;
• Uncontrolled active infections;
• History of immunodeficiency, including positive HIV antibody test；
• Patients with active hepatitis B (HBV titer higher than detection limit) ; hepatitis C virus infection;
• Those with a history of serious cardiovascular disease;
• Patients with other serious systemic disease history who are judged to be unsuitable for clinical trials;
• Alcohol or drug dependence is known;
• Mental disorder or poor compliance;

Sponsors & Collaborators

• Shanghai East Hospital: collaborator
• Dragonboat Biopharmaceutical Company Limited: lead

Study Sites (1)

Dragonboat Biopharmaceutical,Co.,Ltd

Shanghai, Shanghai Municipality, China

Location

Study Officials

• Li Jin, doctor

  Shanghai East Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: April 9, 2019
• Study Start: April 27, 2019
• Primary Completion: April 10, 2023
• Study Completion: April 10, 2023
• Last Updated: July 6, 2026

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)