A Phase I Dose Escalation and Cohort Expansion Study to Evaluate the Safety, Tolerance and Pharmacokinetic of BAT1308 Injection in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- BAT1308
- Conditions
- Advanced Solid Tumor
- Sponsor
- Bio-Thera Solutions
- Enrollment
- 59
- Locations
- 1
- Primary Endpoint
- Explore the maximum tolerated dose (MTD)
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
A phase I dose escalation and cohort expansion study to evaluate the safety, tolerance and pharmacokinetic of BAT1308 injection in patients with advanced solid tumors
Detailed Description
This study is a multicenter, open, dose-increasing and dose-expanding phase I clinical study. The dose increasing method of "3 + 3" is used to explore the safety, tolerance and pharmacokinetic characteristics of BAT1308 injection in patients with advanced solid tumors (12-18 cases). After the completion of dose increment, 300mg tolerated doses were selected for extended research on advanced non-small cell lung cancer, advanced hepatocellular carcinoma and cervical cancer (80-130 cases), so as to provide recommended doses for subsequent clinical trials.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 to 75 years old (including boundary value), male or female;
- •Voluntarily sign informed consent;
- •Research Population:
- •A) Dose escalation stage: patients with advanced malignant solid tumors that have been pathologically confirmed, failed or are intolerant to standard therapy. Agree to provide previously stored tumor tissue samples for PD-L1 testing or existing PD-L1 testing results.
- •B) Dose extension phase: divided into 3 cohorts:
- •i. Cohort A: pathologically confirmed patients with advanced non-small cell lung cancer (NSCLC) who failed standard therapy and who were intolerant or refused standard therapy. And agree to provide previously stored tumor tissue specimens or fresh biopsy of tumor focal tissue for relevant pathological test pD-L1 ≥1% or existing test results show PD-L1≥1%, ii. Cohort B: Patients with advanced hepatocellular carcinoma (HCC) confirmed by pathological or clinical diagnosis, who failed standard therapy, were intolerant or refused standard therapy, had no PD-L1 test requirements, had child-Pugh liver function rating of GRADE A and better grade B (≤7 points), and had no history of hepatic encephalopathy.
- •iii. Queue C: through pathology diagnosed with cervical cancer (pathological type squamous carcinoma or gland scale cancer), the phase of recurrence or metastasis (2018 edition FIGO stage IVB), cervical cancer, the stage of recurrence or metastasis after standard treatment (first-line platinum-based chemotherapy medicine + beacizumab bead sheet resistance treatment) after failure, intolerance, or refused to accept the standard treatment for patients. Agree to provide previously stored tumor tissue samples or fresh biopsy of tumor focus tissue (exemption if no previously stored tumor tissue samples are available and the investigator assesses there is a significant risk of reacquisition).
- •According to recist1.1 standard, there is at least one measurable tumor focus;
- •ECOG score shall be 0 or 1;
- •The investigator assessed the expected survival ≥ 12 weeks;
Exclusion Criteria
- •Have received clinical trial treatment of any other drug or participated in clinical study of medical device within 4 weeks prior to the first drug administration;
- •Prior treatment with immune checkpoint inhibitors (such as pD-1, PD-L1, CTLA-4 and other targeted antibodies) or immune checkpoint agonists (such as ICOS, CD40, CD137, OX40 and other targeted antibodies).
- •Within 4 weeks before the initial administration of the study drug, she had received chemotherapy and radiotherapy (palliative radiotherapy should be completed at least 2 weeks before the initial administration).
- •Have received TCM and/or Proprietary Chinese medicine therapy or immunomodulatory drugs (such as thymosin, interferon, interleukin, etc.) with antitumor effects (according to the instructions) within 2 weeks prior to the first administration of study drugs;
- •Other targeted therapies (such as tyrosine kinase inhibitors) did not exceed 5 half-lives before the first administration;
- •In addition to the tumor that the subject had enrolled in the study, there were other active malignancies within 2 years prior to the first dose. Patients with locally curable tumours (which appear to be cured), such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or carcinoma in situ of the breast, are not excluded.
- •For patients in cohort C:
- •A) have pathological types other than squamous carcinoma and adenosquamous carcinoma (e.g., small cell carcinoma, adenocarcinoma, clear cell carcinoma, sarcoma, etc.).
- •B) The investigator determined that there was clinically significant hydronephrosis of the renal pelvis or ureter that could not be relieved by nephrostomy or urethral stenting.
- •Before the first administration of the study drug, there were still patients with AE caused by previous antitumor therapy \> grade 1 (CTCAE5.0), except for those AE that could not be recovered to ≤ grade 1 as determined by the researcher based on clinical conditions, such as hair loss and fatigue, and which had been in a stable state for a long time;
Arms & Interventions
Single group
First Phase: dose escalation study. It was divided into three dose groups: 100mg, 300mg and 600mg. The safety, tolerance and pharmacokinetics of BAT1308 injection were explored according to the 3+3 dose increasing mode. It is expected that 12-18 cases will be included in the group. Second Phase: dose expansion study. After the completion of dose increment, 300mg tolerated doses were selected for extended research on advanced non-small cell lung cancer, advanced hepatocellular carcinoma and cervical cancer (80-130 cases), so as to provide recommended doses for subsequent clinical trials.
Intervention: BAT1308
Outcomes
Primary Outcomes
Explore the maximum tolerated dose (MTD)
Time Frame: 21 days after first dosing
Tolerance evaluation: Dose-limiting toxicity (DLT) is defined as follows: Patients develop the following AE associated with the study drug between day 1 and day 21 after cycle 1 administration: 1)Non-hematological toxicity of grade ≥3 (nausea, vomiting, and diarrhea were relieved within 3 days after supportive treatment, except for infusion reactions that recovered within 2 hours after symptomatic treatment); 2)Grade ≥4 hematologic toxicity (including grade ≥3 neutropenia with fever; However, grade 4 neutropenia requires a duration of ≥7 days to determine DLT); 3) Grade ≥4 thrombocytopenia or grade 3 thrombocytopenia with bleeding. Safety evaluation indexes: Safety indicators include: vital signs, physical examination, laboratory tests, electrocardiogram, cardiac color ultrasound, adverse events (including immune-related adverse events), etc.
Secondary Outcomes
- To evaluate the pharmacodynamics of BAT1308 injection(126 days after first dosing)
- To evaluate the immunogenicity of BAT1308 injection(126 days after first dosing)
- Preliminary evaluation of the anti-tumor efficacy of BAT1308 injection.(126 days after first dosing)
- To evaluate the PK characteristics of BAT1308 injection(126 days after first dosing)