Clinical trial NCT06139536: Assessment of Safety, Tolerability and Pharmacokinetics With BAT4706 and BAT1308 in Advanced Solid Tumors Patients
Official title: A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BAT4706 Injection Combined With BAT1308 Injection in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Bio-Thera Solutions
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BAT4706 Injection Combined With BAT1308 Injection in Patients With Advanced Solid Tumors.

Detailed description: The goal of this interventional study is to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of BAT4706 injection combined with BAT1308 injection in patients with advanced solid tumors, explore the maximum tolerable dose. The study is generally divided into two stages. In the first stage, the "3+3" dose increasing rule is proposed to explore the safety and tolerability, subject will be given BAT1308 injection and BAT4706 injection through Intravenous infusion in the first four cycles, and then maintain administration of BAT1308 monotherapy after four cycles until 18 cycles; In the second stage, based on the preliminary safety and efficacy results of the previous stage, appropriate doses and tumor types were selected for extended research, in order to further explore the safety and clinical effectiveness of BAT4706 injection and BAT1308 injection in the combined administration mode.

Eligibility criteria: Inclusion Criteria:

* Voluntary signing of informed consent.
* Study population:

  1. Dose increasing stage:Patients with advanced malignant solid tumors who have been pathologically confirmed, have failed to standard treatment, or are intolerant to standard treatment.
  2. Dose expansion stage: Divided into 3 queues:

     1. Queue A: Patient with locally advanced or metastatic non-small cell lung cancer (NSCLC) confirmed by pathology, failed to standard treatment, or are intolerant to standard treatment. And it must meet the following requirements: a) Previous PD-L1 test results have been obtained; Or b) Provide previously stored tumor tissue samples or fresh biopsy tumor lesion tissue for PD-L1 testing at the site before the first medication use;
     2. Queue B: Advanced microsatellite stable (pMMR/MSS) colorectal cancer confirmed by pathology, with disease progression after receiving at least 2 standard chemotherapy regimens/lines, and no liver metastasis or resection/ablation liver metastasis.
     3. Queue C: Patient with Hepatocellular carcinoma confirmed by pathology, refractory to at least 1 line of previous systemic treatment, and intolerant to this treatment.
* An evaluable tumor focus was necessary in the dose escalation stage, and at least one measurable tumor focus in the dose expanding stage(according to RECIST 1.1 standard).
* ECOG should be 0-1 in the dose escalation stage, and be 0-2 in the dose expanding stage.
* The expected survival period is more than 12 weeks base on the evaluation of the investigator.
* Enough organs, bone marrow reserve function.
* Female patients with fertility must undergo a serum pregnancy test during the screening period, and the result is negative. Patient must agree to take effective contraceptive methods to prevent pregnancy.

Exclusion Criteria:

* Have received any other clinical trial treatment or participated in a medical device clinical study within 4 weeks prior to the first administration of the study drug.
* Previously failed to receive CTLA-4 monoclonal antibody treatment.
* Received other tumor treatments within 4 weeks prior to the first administration of the study drug, such as chemotherapy, radiotherapy (palliative radiotherapy must be completed within 2 weeks prior to the first administration), targeted therapy/immunotherapy (with a minimum interval of 4 weeks or at least 5 half-lives, whichever is shorter), hormone therapy (excluding alternative therapy).
* Prior to the first administration of the investigational drug, there were still cases of AE caused by previous anti-tumor therapy that were greater than level 1 (CTCAE5.0).
* Having undergone major surgery (such as craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first administration of the study drug, major surgery is defined as a level 3 or 4 surgery; Individuals with a history of organ transplant surgery.
* Primary central nervous system tumor or symptomatic central nervous system metastasis, meningeal metastasis, or previous history of epilepsy. Excluding patients with central nervous system metastasis who are clinically asymptomatic or have symptoms but have been judged stable by investigator.
* If other malignant tumors have been diagnosed within the past 5 years, or if previous malignant tumors have been cured for less than 5 years, the first pathological diagnosis shall prevail. Except radical skin basal cell carcinoma, skin squamous cell carcinoma or carcinoma in situ (such as breast cancer in situ, cervical carcinoma in situ).
* Severe cardiovascular disease: Heart failure with a New York Heart Association(NYHA) rating of 2 or above, left ventricular ejection fraction (LVEF) less than 50%, unstable arrhythmia or unstable angina, uncontrollable hypertension (defined in this protocol as systolic blood pressure\>150mmHg and/or diastolic blood pressure\>100mmHg after treatment, although the optimal antihypertensive treatment is used).
* Patients with a history of autoimmune diseases (those who undergo thyroid hormone replacement therapy to control stable hypothyroidism can be included in the group); Patients who are using immunosuppressive agents or systemic or absorbable local hormone therapy to achieve immunosuppressive effects (dosage\>10mg/day of prednisone or other therapeutic hormones) and continue to use the study drug within 2 weeks before the first administration.
* Active infections with clinical significance that require intravenous antibiotics, including active pulmonary tuberculosis patients.
* Patients with uncontrolled or requiring drainage of pleural, pericardial, or abdominal effusion.
* Individuals at risk of thrombosis or bleeding.
* Individuals infected with the following diseases: human immunodeficiency virus (HIV) infection; Treponema pallidum antibody positive; Active hepatitis B virus infected; Hepatitis C virus infected.
* Received or planned to receive live/attenuated vaccines within 4 weeks prior to screening or during the study period.
* Known to have experienced severe hypersensitivity reactions to any monoclonal antibody.
* Patients who have a known history of abuse or drug use of psychotropic substances and are believed to affect compliance with this study.
* Pregnant or lactating women.
* The study participants who were considered unsuitable for the study by investigator.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: The first administration cycle(21 days)
measure: Vital signs
timeFrame: Through study completion, 1 year
measure: Physical examination
timeFrame: Through study completion, 1 year
measure: Laboratory Examination
timeFrame: Through study completion, 1 year
measure: Electrocardiogram
timeFrame: Through study completion, 1 year
measure: Echocardiography
timeFrame: Through study completion, 1 year
measure: Adverse event
timeFrame: Through study completion, 1 year
Secondary outcomes:
measure: Pharmacokinetic
timeFrame: Every cycle until 18 cycles (one cycle equals 3 weeks)
measure: Immunogenicity
timeFrame: Every cycle until 18 cycles (one cycle equals 3 weeks)
measure: Objective response rate (ORR)
timeFrame: Through study completion, 1 year
measure: Best Overall Response Rate(BORR)
timeFrame: Through study completion, 1 year
measure: Progression-Free Survival(PFS)
timeFrame: Through study completion, 1 year
measure: Duration of Response(DOR)
timeFrame: Through study completion, 1 year
measure: Overall Survival(OS)
timeFrame: Through study completion, 1 year
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
Study officials:
affiliation: Henan Cancer Hospital
name: Suxia Luo
role: PRINCIPAL_INVESTIGATOR
References: