Assessment of Safety ,Tolerance and Pharmacokinetics Clinical Efficacy With BAT4706 in Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT05148325
• Recruitment Status: Recruiting
• First Posted: December 8, 2021
• Last Update Posted: December 8, 2021
• Sponsor: Bio-Thera Solutions
• Collaborator: Beijing Cancer Hospital
• Information provided by (Responsible Party): Bio-Thera Solutions

Study Description

Brief Summary:

A Phase I Clinical Study to Evaluate the Safety, Tolerance and Pharmacokinetics of BAT4706 Injection in Patients With Advanced Solid Tumors.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumor; Melanoma	Drug: BAT4706	Phase 1

Detailed Description:

This study is a single center, 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 PK characteristics of BAT4706 injection in patients with advanced solid tumors. After the completion of dose increment, 1-2 tolerated doses were selected for extended research on melanoma (20-40 cases), so as to provide recommended doses for subsequent clinical trials.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Clinical Study to Evaluate the Safety, Tolerance and Pharmacokinetics of BAT4706 Injection in Patients With Advanced Solid Tumors
• Actual Study Start Date: September 2, 2021
• Estimated Primary Completion Date: September 22, 2022
• Estimated Study Completion Date: January 20, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Single group; First Phase: dose escalation study. It was divided into four dose groups: 0.1mg/kg, 0.3mg/kg, 0.5mg/kg and 1.0mg/kg. The safety, tolerability and pharmacokinetics of bat4706 injection were explored according to the 3 + 3 dose increasing mode. It is expected that 12-24 cases will be included in the group Second Phase: dose expansion study. After the completion of dose increment, 1-2 tolerated doses were selected for extended research on melanoma (20-40 cases), so as to provide recommended doses for subsequent clinical trials

Drug: BAT4706; The administration cycle was proposed to be 3 weeks (Q3W), i.e., 21 days in a cycle, and the first 4 cycles were administered on the first day of each cycle.

Outcome Measures

Primary Outcome Measures :

1. Explore the maximum tolerated dose (MTD) [ Time Frame: 21 days after first dosing ]
   To evaluate the safety and tolerance of BAT4706 injection in patients with advanced solid tumors, explore the maximum tolerated dose (MTD), and provide the recommended dose for subsequent clinical trials.

Secondary Outcome Measures :

1. Cmax [ Time Frame: 126 days after first dosing ]
   Single dose PK characteristics
2. Tmax [ Time Frame: 126 days after first dosing ]
   Single dose PK characteristics
3. T1/2 [ Time Frame: 126 days after first dosing ]
   PK characteristics
4. CL [ Time Frame: 126 days after first dosing ]
   Single dose PK characteristics
5. Vd [ Time Frame: 126 days after first dosing ]
   Single dose PK characteristics
6. AUC(0-τ) [ Time Frame: 126 days after first dosing ]
   Single dose PK characteristics
7. AUC(0-∞) [ Time Frame: 126 days after first dosing ]
   Single dose PK characteristics
8. Cmax [ Time Frame: 126 days after first dosing ]
   Multiple doses PK characteristics
9. Tmax [ Time Frame: 126 days after first dosing ]
   Multiple doses PK characteristics
10. T1/2 [ Time Frame: 126 days after first dosing ]
    Multiple doses PK characteristics
11. CL [ Time Frame: 126 days after first dosing ]
    Multiple doses PK characteristics
12. MRT [ Time Frame: 126 days after first dosing ]
    Multiple doses PK characteristics
13. DF [ Time Frame: 126 days after first dosing ]
    Multiple doses PK characteristics
14. ADA antibody [ Time Frame: 126 days after first dosing ]
    immunogenicity
15. Nab positive [ Time Frame: 126 days after first dosing ]
    immunogenicity
16. ORR [ Time Frame: 126 days after first dosing ]
    Tumor evaluation after administration will be performed at weeks 6, 12, and 18.
17. BORR [ Time Frame: 126 days after first dosing ]
    Tumor evaluation after administration will be performed at weeks 6, 12, and 18.
18. DOR [ Time Frame: 126 days after first dosing ]
    Tumor evaluation after administration will be performed at weeks 6, 12, and 18.
19. PFS [ Time Frame: 126 days after first dosing ]
    Tumor evaluation after administration will be performed at weeks 6, 12, and 18.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 18 to 75 years old (including boundary value), male or female;
• Voluntarily sign informed consent;
• Study population: advanced patients diagnosed by pathology and without effective standard treatment or standard treatment failure or standard treatment intolerance.Patients with malignant solid tumors. (the extended study phase is mainly for patients with advanced melanoma);
• 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;
• Have sufficient organ and bone marrow functions as below:Blood routine (no blood transfusion, no hematopoietic stimulator, and no medication to correct blood count within 14 days prior to first dosing),Neutrophil absolute count (ANC) ≥1.5×109 /L, Platelet count ≥75×109/L, Hemoglobin ≥90g/L, Blood coagulation function Prothrombin time (PT) or International standardized ratio (INR) and activated partial thrombin time (APTT) ≤ 1.5×ULN, Liver function Total bilirubin (TBIL) ≤2×ULN ,Alanine aminotransferase (ALT), aspartate aminotransferase (AST) -- ≤3×ULN,Serum Creatinine ≤1.5×ULN ，renal function Serum creatinine clearance rate & GT; 60ml/min (Cockcroft-Gault formula, see appendix)
• Female patients with fertility must have negative serum pregnancy test during screening, and agree to take effective birth control / contraception to prevent pregnancy from the study period to 6 months after the last administration. Male patients must agree to take effective contraceptive methods from the study period to 6 months after the last administration.

Exclusion Criteria:

• Have received experimental drug treatment or participated in clinical research of medical devices within 4 weeks before the first administration of study drugs Research;
• Received chemotherapy and radiotherapy within 4 weeks before the first administration of the study drug (palliative radiotherapy shall be completed within 2 weeks before the first administration),Chinese traditional medicine and Chinese patent medicine with anti-tumor effect (judged according to the instructions), and other targeted therapies such as tyramine Acid kinase inhibitor, immunotherapy (the interval between the last treatment and the first study drug treatment is at least 4 weeks or 5 half lives,Whichever is longer, etc.);
• Failure of CTLA-4 monoclonal antibody treatment in the past;
• Before the first administration of the study drug, the AE (ctcae5.0) caused by previous antitumor treatment was still > grade 1, hair loss and menstrual stimulation Except those with stable immune hypothyroidism controlled by hormone replacement therapy;
• Received interventional therapy and major surgery (such as craniotomy, thoracotomy or laparotomy) within 4 weeks before the first administration of the study drug;Surgery is defined here as grade 3 and 4 surgery;
• Have a history of organ transplantation;
• Central nervous system or meningeal metastasis;
• If other malignant tumors have been diagnosed in recent 5 years, or the previous malignant tumors have been cured for less than 5 years, the time of the first pathological diagnosis shall prevail Subject to. Except for radical skin basal cell carcinoma, cutaneous squamous cell carcinoma or in situ carcinoma, such as in situ breast cancer, Cervical carcinoma in situ);
• Patients with ocular melanoma;
• Patients with esophageal or gastric variceal bleeding in the past 6 months, or the investigator assessed the risk of bleeding;
• Serious cardiovascular disease occurred within 6 months before the first medication: the New York Heart Association rating (NYHA) is 2 Heart failure of grade and above, left ventricular ejection fraction (LVEF) < 50%, unstable arrhythmia or unstable heart Colic and uncontrollable hypertension (this protocol is defined as contraction after treatment despite optimal antihypertensive treatment Blood pressure > 150mmhg and / or diastolic blood pressure > 100mmhg, and the investigator's evaluation is of clinical significance);
• Patients with a history of autoimmune diseases; Had splenectomy or splenic irradiation;
• Drugs with immunomodulatory effect (e.g. thymosin, interferon, interleukin) were used within 2 weeks before the first administration of the study drug Hormone) or hormone (equivalent dose > prednisone 10mg / day);
• Patients with active tuberculosis; Active infections requiring intravenous antibiotic treatment;
• People infected with the following diseases: human immunodeficiency virus (HIV) infection; Treponema pallidum antibody positive; hepatitis B virus Infected persons were positive for hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) and hepatitis B virus deoxyribonucleic acid.

Acid (HBV DNA) detection > 2000iu / ml (or 1 × 104 copies / ml); HCV infected persons [HCV antibody and disease];Viral RNA (HCV RNA) test results were positive];

• Inoculated within 4 weeks before the first medication, or planned to receive live / attenuated vaccine during the study period;
• Known hypersensitivity to any monoclonal antibody;
• Known history of psychotropic substance abuse or drug abuse;
• Pregnant or lactating women;
• Other patients considered by the investigator as unsuitable to participate in this study.

Contacts and Locations

Contacts

Contact: Yu Sun; 15040223137; yusun@bio-thera.com

Contact: Zhaohe Wang, Ph.D; 86-020-32203220; zhwang@bio-thera.com

Locations

China

Beijing cancer hospital; Recruiting

Beijing, China

Contact: Jun Guo, Ph.D

Sponsors and Collaborators

Bio-Thera Solutions

Beijing Cancer Hospital

Investigators

• Principal Investigator: Jun Guo, M.D; Beijing Cancer Hospital

More Information

• Responsible Party: Bio-Thera Solutions
• ClinicalTrials.gov Identifier: NCT05148325
• Other Study ID Numbers: BAT-4706-001-CR
• First Posted: December 8, 2021
• Last Update Posted: December 8, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas