A Clinical Study to Evaluate Single-agent Therapy of BR113 for Injection in Patients With Advanced Solid Tumors

Official title

A Multicenter, Open-label, Two-stage Phase I Clinical Study to Evaluate the Safety, Tolerability and Efficacy of BR113 in Patients With Advanced Solid Tumors

Overview

This is a Phase I, multicenter, open-label, single-arm and first-in-human clinical study of BR113 for injection. The study objectives are to evaluate the safety, tolerability, pharmacokinetic profile, anti-tumor activity and immunogenicity of BR113 for injection in patients with advanced malignancies.

Interventions

• Drug BR113 for injection
  Dosage and Administration: BR113 for Injection is administered intravenously as monotherapy . Treatment shall continue until the occurrence of intolerable toxicity, disease progression, death, or subject withdrawal from study treatment

Primary outcome measures

• DLT（Phase 1a） [Time frame: up to 21 days after first dose of BR113]
• Treatment-emergent adverse events (Phase 1a) [Time frame: Baseline through study completion (30 days after last dose), up to approximately 20 months.]
• RP2D (Phase 1b) [Time frame: Through study completion, approximately 3 years.]

Secondary outcome measures (6)

• Objective response rate (ORR) [Time frame: Up to approximately 3 years]
• Progression-free survival (PFS) [Time frame: Up to approximately 3 years]
• Peak Plasma Concentration (Cmax) [Time frame: Up to approximately 3 years]
• Area under the plasma concentration versus time curve (AUC) [Time frame: Up to approximately 3 years]
• Terminal half-life (T1/2) [Time frame: Up to approximately 3 years]
• The anti-drug antibody (ADA) of BR113 [Time frame: Baseline through study completion(30 days after last dose)，Up to approximately 3 years]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the Informed Consent Form (ICF), understand the nature, purpose, and procedures of the trial, and agree to complete the trial in accordance with the protocol.
• Age ≥ 18 years (as of the date of ICF signing), with no restriction on gender.
• Have histologically and/or cytologically confirmed unresectable, advanced/metastatic solid tumor that is refractory to standard therapy (disease progression or recurrence during or after treatment), intolerant to standard therapy, or for whom no available standard therapy exists.
• Have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Echocardiogram (ECHO) performed within 28 days prior to the first dose shows left ventricular ejection fraction (LVEF) ≥ 50%.
• Adverse events related to prior anti-tumor therapy have recovered to Grade 0-1 per Common Terminology Criteria for Adverse Events (CTCAE),.
• Adequate bone marrow function within 14 days prior to the first dose.
• Adequate organ function within 14 days prior to the first dose.
• Sufficient washout period from prior therapy before the first dose.
• Expected survival ≥ 12 weeks.
• Study participants must provide archival tumor resection specimens (preferably collected within 2 years) or receive tumor tissue biopsy.
• Female participants of childbearing potential (WOCBP) must have a negative serum human chorionic gonadotropin (HCG) test at study entry (within 72 hours before the first dose), and agree to practice true abstinence or use highly effective contraception from the date of signing the ICF until 6 months after the last dose of study treatment. They must not donate germ cells for assisted reproductive purposes during this period.
• Male participants must voluntarily practice abstinence or use highly effective contraception from the date of signing the ICF until 6 months after the last dose, and must not donate sperm for assisted reproductive purposes during this period.

Exclusion criteria

• History of hypersensitivity to any component or excipient of BR113 Injection.
• Prior therapy with Trop-2-targeted agents (including antibodies or ADCs), exatecan, or ADC drugs with exatecan as the payload.
• Prior therapy with STING pathway agents (including STING agonists and STING inhibitors).
• Active infection requiring systemic therapy within 2 weeks prior to the first dose; excluding patients receiving short-term antibiotic prophylaxis (e.g., for urinary tract infection or exacerbation of chronic obstructive pulmonary disease).
• Unstable pleural effusion or ascites requiring thoracentesis or paracentesis within 2 weeks prior to the first dose.
• Major organ surgery within 4 weeks prior to the first dose, or elective surgery planned during the trial.
• Vaccination with live attenuated vaccine within 4 weeks prior to the first dose.
• History of other primary malignant tumors (excluding the study disease) within 5 years prior to enrollment; excluding curatively resected non-melanoma skin cancer (e.g., basal or squamous cell carcinoma) and curatively resected carcinoma in situ (e.g., cervical or breast carcinoma in situ).
• Uncontrolled or severe cardiovascular/cerebrovascular disease.
• Severe pulmonary disease.
• History of severe hematological toxicity during prior systemic therapy (e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3-4 neutropenia).
• Active CNS metastases (defined as symptomatic CNS metastases without anti-tumor therapy \[e.g., radiotherapy\] or requiring corticosteroid/anticonvulsant therapy).
• Active gastrointestinal bleeding or intestinal obstruction.
• Prior allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Poorly controlled diabetes mellitus or history of diabetic ketoacidosis.
• Thromboembolism requiring anticoagulant therapy diagnosed within 6 months prior to enrollment, or known hereditary or acquired bleeding diathesis (e.g., hemophilia, coagulation disorder); excluding low-dose prophylactic anticoagulation (e.g., low-molecular-weight heparin).
• Active keratitis or conjunctivitis.
• Systemic corticosteroid therapy for > 1 week within 2 weeks prior to the first dose (methylprednisolone > 10 mg/day or equivalent dose of other similar drugs).
• Use of immunosuppressants within 2 weeks prior to the first dose, active autoimmune disease, or history of autoimmune disease.
• Human Immunodeficiency Virus (HIV) infection (seropositive) or Acquired Immunodeficiency Syndrome (AIDS).
• Positive non-specific syphilis antibody test (e.g., TRUST, PRP) or positive specific syphilis antibody test (e.g., TPPA).
• Active tuberculosis or anti-tuberculosis treatment within 1 year prior to enrollment.
• HBsAg-positive with HBV-DNA > 1000 IU/mL.
• HBcAb-positive with HCV-RNA above the study site's lower limit of detection.
• Any psychiatric or cognitive disorder that may limit understanding or execution of the ICF.
• Pregnant or lactating females (excluding females who voluntarily discontinue breastfeeding).
• Participants deemed ineligible for enrollment by the investigator or unable to complete the trial for other reasons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07753590 · BR113-CR-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗