Clinical Trial of TQB2868 Injection in Subjects With Advanced Malignant Tumors

NCT05198505
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Phase
Phase 1
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Recruitment status
Unknown
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Participants
280
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Lead sponsor
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.
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Start date
2022-04-27
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Number of sites
3
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Summary
The TQB2868 protein in this study targeted programmed cell death protein 1 (PD-1) and transforming growth factor-β (TGF-β). The bifunctional fusion protein targets and neutralizes TGF-β in the tumor microenvironment. On the basis of inhibiting PD-1 / programmed death ligand 1 (PD-L1) pathway, T cells can restore activity, enhance immune response, and more effectively improve the effect of inhibiting tumor occurrence and development.
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Short title
Clinical Trial of TQB2868 Injection in Subjects With Advanced Malignant Tumors
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Official title
Phase I Clinical Trial to Evaluate the Tolerability and Pharmacokinetics of TQB2868 Injection in Subjects With Advanced Malignant Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Unknown
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Phase
Phase 1
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Study type
Interventional
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Completion date
2024-06-01
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First posted
2022-01-20
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Registry last updated
2022-05-02
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Primary completion date
2023-06-01
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Start date
2022-04-27
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Participants
280
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Participant count basis
Estimated
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Planned participants
280
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Protocol amendments
0
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Number of sites
3
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Registry sponsor category
Industry
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Lead sponsor
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05198505
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ClinicalTrials.gov ID
NCT05198505
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Registry record
Open registry record
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Allocation
Not applicable
Model
Single group
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Dose-limiting toxicity (DLT)

    Timeframe: up to 10 months

    DLT definition: the subject has the following adverse events related to the test drug within one treatment cycle (21 days) after the first administration. 1. Grade ≥ 3 neutropenia with fever; Grade 4 neutropenia that cannot be recovered within 3 days after symptomatic treatment; Grade 3 anemia that cannot be recovered within 14 days; ≥ Grade 3 thrombocytopenia with bleeding; Other hematological toxicity above grade 4 (inclusive); 2. ≥ Grade 3 non hematological toxicity; Nausea, vomiting, diarrhea, rash and electrolyte disorder that cannot be recovered to grade ≤ 2 within 7 days after symptomatic treatment; Grade 3 general fatigue, fatigue and headache with duration ≥ 7 days; Laboratory examination abnormalities with isolated ≥ grade 3 and significant clinical symptoms; 3. Adverse events related to ≥ grade 3 infusion reaction occurred, and did not return to normal within 6 hours after stopping infusion

  2. Recommended Phase II Dose (RP2D)

    Timeframe: up to 10 months

    To evaluate RP2D of TQB2868 injection in adult patients with advanced malignant tumors

  3. Maximum Tolerated Dose (MTD)

    Timeframe: up to 10 months

    Defined as the highest dose when dose-limiting toxicity (DLT) occurred in less than 33% of subjects.

  4. All adverse events (AE), serious adverse events (SAE), and treatment-related adverse events (TEAEs)

    Timeframe: up to 17 months

    ncidence of all adverse events (AE), serious adverse events (SAE), and treatment-related adverse events (TEAEs)

  1. Time to reach maximum(peak )plasma concentration following drug administration (Tmax)

    Timeframe: up to 17 months

    To characterize the pharmacokinetics of TQB2868 by assessment of time to reach maximum plasma concentration after single and multiple dosing

  2. Maximum (peak) plasma drug concentration (Cmax)

    Timeframe: up to 17months

    Cmax is the maximum plasma concentration of TQB2868.

  3. Maximum (peak) steady-state plasma drug concentration during a dosage interval (Css-max)

    Timeframe: up to 17 months

    Cmax is the steady state maximum concentration of TQB2868 .

  4. Title：The plasma concentration time curve at steady state, from 0 to τ area under curve of time. (AUC0-τ)

    Timeframe: up to 17 months

    To characterize the pharmacokinetics of TQB2868 by assessment of area under the plasma concentration time curve from the first dose to a certain time point.

  5. Area under the plasma concentration-time curve from time zero to time t (AUC0-t)

    Timeframe: up to 17 months

    To characterize the pharmacokinetics of TQB2868 by assessment of area under the plasma concentration time curve from the first dose to a certain time point.

  6. Area under the plasma concentration-time curve from time zero to infinity(AUC0-∞)

    Timeframe: up to 17 months

    To characterize the pharmacokinetics of TQB2868 by assessment of area under the plasma concentration time curve from the first dose to infinity.

  7. Apparent total clearance of the drug from plasma after oral administration (CL/F)

    Timeframe: up to 17 months

    CL/F is total clearance rate for TQB2868.

  8. Elimination half-life (t1/2)

    Timeframe: up to 17 months

    t1/2 is time it takes for the blood concentration of TQB2868 to drop by half.

  9. Apparent volume of distribution of intravenous infusion(Vss/F)

    Timeframe: up to 17 months

    Steady-state apparent volume of distribution of TQB2868 injection by intravenous infusion

  10. Elimination rate constant(λ)

    Timeframe: up to 17 months

    λ is the elimination rate constant when TQB2868 participates in the calculation of metabolism in the body

  11. Area under the plasma concentration-time curve from time zero to time 24h.( AUC0-24h)

    Timeframe: up to 17 months

    Characterize the pharmacokinetics of TQB2868 by evaluating the area under the plasma concentration-time curve from the first administration to 24h

  12. Mean residence time (MRT)

    Timeframe: up to 17 months

    MRT describes the average time that TQB2868 remains in the body.

  13. Minimum steady-state plasma drug concentration during a dosage interval (Css-min)

    Timeframe: up to 17 months

    Css-min is the minimum plasma concentration of TQB2868.

  14. Degree of fluctuation(DF)

    Timeframe: up to 17 months

    DF is the volatility coefficient of TQB2868.

  15. Average steady-state plasma drug concentration during multiple-dose administration (Css-avg)

    Timeframe: up to 17 months

    Css-avg is the average of steady-state plasma concentration of TQB2868 .

  16. Anti-drug antibodies(ADA)

    Timeframe: up to 17 months

    ADA is antibodies that make TQB2868 clear in the body quickly

  17. Receptor Occupancy(RO)

    Timeframe: up to 17 months

    RO is a receptor occupancy for TQB2868 involved in metabolism in the body

  18. Progression-free survival (PFS)

    Timeframe: up to 29 months

    PFS is defined as the time from the first treatment to the first disease progression or death from any cause

  19. Overall response rate (ORR)

    Timeframe: up to 29 months

    Percentage of participants achieving complete response (CR) and partial response (PR).

  20. Disease control rate（DCR）

    Timeframe: up to 29 months

    Percentage of participants achieving CR and PR and stable disease (SD).

  21. Duration of Response (DOR)

    Timeframe: up to 29 months

    The period from the participants first achieving CR or PR to disease progression.

  22. Overall survival (OS)

    Timeframe: up to 29 months

    OS is defined as the time from the first administration to all-cause death.

  23. PD-L1 expression in tumor tissue

    Timeframe: up to 17 months

    To evaluate the expression of PD -L1

  24. TGF-β expression in blood samples

    Timeframe: up to 17 months

    To evaluate the expression of TGF-β

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
75 Years
Healthy volunteers
No

  • 1 Subjects voluntarily join the study and sign an informed consent form.
  • 2 Age: 18-75 years old (when signing the informed consent form); Eastern Cooperative Oncology Group Performance status (ECOG PS) score: 0~1 points.
  • 3 Advanced malignant tumors clearly diagnosed by histology or cytology.
  • 4 Patients with advanced malignant tumors who have been diagnosed by tissue and/or cytology and have failed standard treatments or lack effective treatment options.
  • 5 The main organs are in good function, and the following examination results are good: routine blood examination, biochemical examination, blood coagulation function examination, heart color Doppler ultrasound evaluation.
  • 6 Female subjects of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study period and within 6 months after the end of the study; serum pregnancy/urine within 7 days before study entry The pregnancy test is negative and must be a non-lactating subject; male subjects should agree that contraception must be used during the study period and within 6 months after the end of the study period.

  • 1 Combined diseases and medical history:

    1. Has had other malignant tumors within 3 years before the first medication. The following two conditions can be included in the group: other malignant tumors treated with a single operation to achieve disease-free survival (DFS) for 5 consecutive years; cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors [ Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)];
    2. Unrelieved toxic reactions higher than Common Terminology Criteria Adverse Events (CTC AE) level 1 or higher caused by any previous treatment, excluding hair loss;
    3. Major surgical treatment, obvious traumatic injury or long-term unhealed wounds or fractures have been received within 28 days before the first medication;
    4. Arterial/venous thrombosis occurred within 6 months before the first administration, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
    5. Existence of active pulmonary tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonia requiring treatment or active pneumonia with clinical symptoms;
    6. People who have a history of psychotropic drug abuse and cannot be quit or have mental disorders;
    7. Previous recipients of allogeneic bone marrow transplantation or solid organ transplantation.
    8. Subjects with any severe and / or uncontrolled disease.

  • 2 Tumor-related symptoms and treatment:

    1. Have received chemotherapy, radiotherapy or other anti-cancer therapies within 4 weeks before the first medication (the washout period will be calculated from the end of the last treatment); if you have received local radiotherapy in the past, you can join the group if the following conditions are met: End of radiotherapy more than 4 weeks from the start of the study treatment (brain radiotherapy is more than 2 weeks); and the target lesion selected for this study is not in the radiotherapy area; or the target lesion is located in the radiotherapy area, but progress has been confirmed.
    2. Received Chinese patent medicine treatment with anti-tumor indications specified in the National Medical Products Administration (NMPA) approved drug instructions within 2 weeks before the first medication;
    3. Have previously received immunological double-antibody therapeutic drugs against the same target of TQB2868 injection;
    4. Uncontrollable pleural effusion, pericardial effusion or ascites that still needs to be drained repeatedly (investigator's judgment);
    5. Known to have spinal cord compression, cancerous meningitis, accompanied by brain metastasis symptoms, or symptom control time less than 2 weeks;

  • 3 Research and treatment related:

    1. The history of live attenuated vaccine vaccination within 28 days before the first administration or the planned live attenuated vaccine vaccination during the research period;
    2. Those who have had severe hypersensitivity reactions after using macromolecular drugs;
    3. An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, corticosteroids, or immunosuppressive agents) occurred within 2 years before the first medication. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;
    4. Diagnosed with immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose>10mg/day prednisone or other curative hormones), and continue within 2 weeks of the first administration in use;

  • 4 Participated in other anti-tumor drug clinical trials within 4 weeks before the first medication;

  • 5 According to the judgment of the researcher, there are situations that seriously endanger the safety of the subjects or affect the completion of the research by the subjects.

Sources for eligibility
clinicaltrials.gov

  • Henan Cancer HospitalZhengzhou, ChinaRecruiting
  • Linyi Cancer HospitalLinyi, ChinaRecruiting
  • Shanghai Pulmonary HospitalShanghai, ChinaRecruiting
Sources for sites
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Related records

Drugs (1)

Lead sponsors (1)

Conditions (1)