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

Phase I Clinical Trial to Evaluate the Safety, Tolerance and Pharmacokinetics of Human Anti-PD-L1 Monoclonal Antibody Injection (LDP) in Patients With Advanced Malignant Tumors

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.

Study Overview

• Status: Unknown
• Conditions: Advanced Tumors
• Intervention / Treatment: Drug: Whole Human Anti-PD-L1 Antibody Injection (LDP)

Detailed Description

This trial is an open, dose escalation phase I clinical trial study of patients with advanced cancer who have failed standard treatment. The trial is divided into a dose escalation phase and an expansion phase.

Approximately 130 patients will be enrolled in this trial. The dose-increasing phase is about 30 cases, and the expansion stage is about 100 cases.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Dragonboat Biopharmaceutical,Co.,Ltd
      • Contact: ZHANG XIAOLEI, DOCTOR; Phone Number: (+86)02150276381; Email: xiaolei.zhang@dragonboatbio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 (inclusive), regardless of gender
2. 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;
3. The estimated survival time is more than 3 months.
4. At least one assessable tumor lesion (solid tumors according to RECIST 1.1, lymphoma according to Lugano 2014);
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=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;

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; female patients of childbearing age are selected before the election. The blood or urine pregnancy test within the day must be negative;
8. Prior to the trial, the subject shall have informed consent to the study and voluntarily sign a written form of 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 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；
2. Major organ surgery (excluding puncture biopsy) or significant trauma occurred within 4 weeks before the first administration.
3. 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).
4. 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;
5. Those who have previously received treatment with PD-1 or PD-L1 inhibitors;
6. In the past, immune-related adverse events (> grade 3) have occurred in immunotherapy (irAE, see Appendix 5)；
7. Patients with active or recurrent autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.)；
8. Current or previous patients with interstitial lung disease;
9. Uncontrolled active infections;
10. History of immunodeficiency, including positive HIV antibody test；
11. Patients with active hepatitis B (HBV titer higher than detection limit) ; hepatitis C virus infection;
12. Those with a history of serious cardiovascular disease;
13. Patients with other serious systemic disease history who are judged to be unsuitable for clinical trials;
14. Alcohol or drug dependence is known;
15. Mental disorder or poor compliance;
16. Pregnant or lactating women;
17. Acceptance of live attenuated vaccine within 4 weeks before the first administration or during the study period is planned.
18. Researchers believe that there are any abnormal clinical or laboratory examinations or other reasons in the subjects and that they are not suitable for this clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug: LDP; 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); Dose escalation study evaluating six dose levels (0.1, 0.3, 1, 3 , 10and 20 mg/kg) of LDP.; Other Names: LDP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters: Observed Maximum Serum Concentration (Cmax) of LDP After Infusion	Pharmacokinetic parameters Cmax for LDP	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	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	Pharmacokinetic parameters: AUC(0-00) for LDP	Up to 22 Days
Pharmacokinetic parameters: Apparent Terminal Half-life (t1/2) of LDP After Infusion	Pharmacokinetic parameters T1/2 for LDP	Up to 22 Days
Immunogenicity indicators: Number of participants with positive anti-drug antibodies (ADA)	Immunogenicity indicators: Number of participants with positive anti-drug	Up to 176 Days
Immunogenicity indicators: Number of participants with positive neutralizing antibodies	Immunogenicity indicators: Number of participants with positive neutralizing antibodies	Up to 176 Days
Objective response rate (ORR)	The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.	From first dose of LDP through 21 days after last dose of LDP up to 2 years.
Progression-free survival (PFS)	Progression-free survival is defined as the time from the start of treatment with LDP until the first documentation of disease progression or death due to any cause, whichever occurs first.	From first dose of LDP through 21 days after last dose of LDP up to 2 years.

Collaborators and Investigators

• Sponsor: Dragonboat Biopharmaceutical Company Limited
• Collaborators: Shanghai East Hospital
• Investigators: Study Chair: Li Jin, doctor, Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2019
• Primary Completion (Anticipated): November 26, 2021
• Study Completion (Anticipated): April 26, 2022

Study Registration Dates

• First Submitted: April 8, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (Actual): April 9, 2019

Study Record Updates

• Last Update Posted (Actual): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: LDP100001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No