Clinical trial NCT05198505: Clinical Trial of TQB2868 Injection in Subjects With Advanced Malignant Tumors
Official title: Phase I Clinical Trial to Evaluate the Tolerability and Pharmacokinetics of TQB2868 Injection in Subjects With Advanced Malignant Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Malignant Tumor
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-01-20
Enrollment: 280
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: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: up to 10 months
measure: Recommended Phase II Dose (RP2D)
timeFrame: up to 10 months
measure: Maximum Tolerated Dose (MTD)
timeFrame: up to 10 months
measure: All adverse events (AE), serious adverse events (SAE), and treatment-related adverse events (TEAEs)
timeFrame: up to 17 months
Secondary outcomes:
measure: Time to reach maximum(peak )plasma concentration following drug administration (Tmax)
timeFrame: up to 17 months
measure: Maximum (peak) plasma drug concentration (Cmax)
timeFrame: up to 17months
measure: Maximum (peak) steady-state plasma drug concentration during a dosage interval (Css-max)
timeFrame: up to 17 months
measure: 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
measure: Area under the plasma concentration-time curve from time zero to time t (AUC0-t)
timeFrame: up to 17 months
measure: Area under the plasma concentration-time curve from time zero to infinity(AUC0-∞)
timeFrame: up to 17 months
measure: Apparent total clearance of the drug from plasma after oral administration (CL/F)
timeFrame: up to 17 months
measure: Elimination half-life (t1/2)
timeFrame: up to 17 months
measure: Apparent volume of distribution of intravenous infusion(Vss/F)
timeFrame: up to 17 months
measure: Elimination rate constant(λ)
timeFrame: up to 17 months
measure: Area under the plasma concentration-time curve from time zero to time 24h.( AUC0-24h)
timeFrame: up to 17 months
measure: Mean residence time (MRT)
timeFrame: up to 17 months
measure: Minimum steady-state plasma drug concentration during a dosage interval (Css-min)
timeFrame: up to 17 months
measure: Degree of fluctuation(DF)
timeFrame: up to 17 months
measure: Average steady-state plasma drug concentration during multiple-dose administration (Css-avg)
timeFrame: up to 17 months
measure: Anti-drug antibodies(ADA)
timeFrame: up to 17 months
measure: Receptor Occupancy(RO)
timeFrame: up to 17 months
measure: Progression-free survival (PFS)
timeFrame: up to 29 months
measure: Overall response rate (ORR)
timeFrame: up to 29 months
measure: Disease control rate（DCR）
timeFrame: up to 29 months
measure: Duration of Response (DOR)
timeFrame: up to 29 months
measure: Overall survival (OS)
timeFrame: up to 29 months
measure: PD-L1 expression in tumor tissue
timeFrame: up to 17 months
measure: TGF-β expression in blood samples
timeFrame: up to 17 months
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
References: