Assessment of Safety, Tolerability and Pharmacokinetics With BAT4706 and BAT1308 in Advanced Solid Tumors Patients

NCT06139536 | Recruiting Phase 1

• 1 other identifier: BAT-4706-1308-001-CR
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (7)

• Dose-limiting toxicity (DLT)

  The following AEs related to the study drug occurred from day 1 to day 21 after administration in the first cycle: ≥grade 3 of non hematological toxicity (except for nausea, vomiting, and diarrhea that can be relieved within 3 days of supportive treatment, and those who recover within 2 hours of symptomatic treatment of infusion reactions); ≥grade 4 of Hematological toxicity(including ≥ 3 grade neutropenia with fever; however, grade 4 neutropenia requires a duration of ≥ 7 days to determine DLT);≥ grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding.

  The first administration cycle(21 days)

• Vital signs

  Number of cases with abnormal vital signs results

  Through study completion, 1 year

• Physical examination

  Number of cases with abnormal physical examination results

  Through study completion, 1 year

• Laboratory Examination

  Number of cases with abnormal laboratory examination results

  Through study completion, 1 year

• Electrocardiogram

  Number of cases with abnormal electrocardiogram results

  Through study completion, 1 year

• Echocardiography

  Number of cases with abnormal echocardiography results

  Through study completion, 1 year

• Adverse event

  Number of cases with all adverse medical events that occur after the subject receives the investigational drug assessed by CTCAE V5.0

  Through study completion, 1 year

Secondary Outcomes (7)

• Pharmacokinetic

  Every cycle until 18 cycles (one cycle equals 3 weeks)

• Immunogenicity

  Every cycle until 18 cycles (one cycle equals 3 weeks)

• Objective response rate (ORR)

  Through study completion, 1 year

• Best Overall Response Rate(BORR)

  Through study completion, 1 year

• Progression-Free Survival(PFS)

  Through study completion, 1 year

Study Arms (5)

A/ Standard 3+3 1.0mg/kg of BAT4706 with 300mg of BAT1308

EXPERIMENTAL

Drug: BAT4706 injection, Dosage: 1.0mg/kg, Frequency: once every 3 weeks, Duration: 3 month. Drug: BAT1308 injection, Dosage: 300mg, Frequency: once every 3 weeks, Duration: 1 year.

Drug: BAT4706 Injection; Drug: BAT1308 Injection

B/ Standard 3+3 2.0mg/kg of BAT4706 with 300mg of BAT1308

EXPERIMENTAL

Drug: BAT4706 injection, Dosage: 2.0mg/kg, Frequency: once every 3 weeks, Duration: 3 month. Drug: BAT1308 injection, Dosage: 300mg, Frequency: once every 3 weeks, Duration: 1 year.

Drug: BAT4706 Injection; Drug: BAT1308 Injection

C/ Standard 3+3 3.0mg/kg of BAT4706 with 300mg of BAT1308

EXPERIMENTAL

Drug: BAT4706 injection, Dosage: 3.0mg/kg, Frequency: once every 3 weeks, Duration: 3 month. Drug: BAT1308 injection, Dosage: 300mg, Frequency: once every 3 weeks, Duration: 1 year.

Drug: BAT4706 Injection; Drug: BAT1308 Injection

D/ Standard 3+3 6.0mg/kg of BAT4706 with 300mg of BAT1308

EXPERIMENTAL

Drug: BAT4706 injection, Dosage: 6.0mg/kg, Frequency: once every 3 weeks, Duration: 3 month. Drug: BAT1308 injection, Dosage: 300mg, Frequency: once every 3 weeks, Duration: 1 year.

Drug: BAT4706 Injection; Drug: BAT1308 Injection

E/ Standard 3+3 10.0mg/kg of BAT4706 with 300mg of BAT1308

EXPERIMENTAL

Drug: BAT4706 injection, Dosage: 10mg/kg, Frequency: once every 3 weeks, Duration: 3 month. Drug: BAT1308 injection, Dosage: 300mg, Frequency: once every 3 weeks, Duration: 1 year.

Drug: BAT4706 Injection; Drug: BAT1308 Injection

Interventions

BAT4706 Injection DRUG

Intravenous infusion, 3 weeks one cycle(Q3W), Administer on the first day of each cycle. In the first four cycles, administration starting with BAT1308, and then administering BAT4706 on the same day. Maintain administration of BAT1308 monotherapy after four cycles.

Also known as: Fc-glycosylated recombinant fully humanized anti-CTLA-4 monoclonal antibody injection

A/ Standard 3+3 1.0mg/kg of BAT4706 with 300mg of BAT1308; B/ Standard 3+3 2.0mg/kg of BAT4706 with 300mg of BAT1308; C/ Standard 3+3 3.0mg/kg of BAT4706 with 300mg of BAT1308; D/ Standard 3+3 6.0mg/kg of BAT4706 with 300mg of BAT1308; E/ Standard 3+3 10.0mg/kg of BAT4706 with 300mg of BAT1308

BAT1308 Injection DRUG

Intravenous infusion, 3 weeks one cycle(Q3W), Administer on the first day of each cycle. In the first four cycles, administration starting with BAT1308, and then administering BAT4706 on the same day. Maintain administration of BAT1308 monotherapy after four cycles.

Also known as: Recombinant humanized anti PD-1 monoclonal antibody injection

A/ Standard 3+3 1.0mg/kg of BAT4706 with 300mg of BAT1308; B/ Standard 3+3 2.0mg/kg of BAT4706 with 300mg of BAT1308; C/ Standard 3+3 3.0mg/kg of BAT4706 with 300mg of BAT1308; D/ Standard 3+3 6.0mg/kg of BAT4706 with 300mg of BAT1308; E/ Standard 3+3 10.0mg/kg of BAT4706 with 300mg of BAT1308

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary signing of informed consent.
• Study population:
• 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.
• Dose expansion stage: Divided into 3 queues:
• 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;
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bio-Thera Solutions: lead

Study Sites (3)

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

RECRUITING

The First Affiliated Hospital of Henan University of Science and Technology

Zhengzhou, Henan, 450052, China

NOT YET RECRUITING

Linyi Cancer Hospital

Linyi, Shandong, 276002, China

NOT YET RECRUITING

Study Officials

• Suxia Luo

  Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cuiyu Li

CONTACT

15068858368; cyli@bio-thera.com

Zhaohe Wang

CONTACT

13318818667; Zhwang@bio-thera.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: November 18, 2023
• Study Start: March 6, 2024
• Primary Completion: December 1, 2025
• Study Completion: February 1, 2026
• Last Updated: March 13, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)