The trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of B4t2-001.
The first patient has been dosed in a phase 1 clinical trial (NCT05621486) evaluating Bio4t2’s B4t2-001, an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy, for the treatment of advanced solid tumors.
B4t2-001 is intended to target the self-antigen BT-001. It is based on Bio4t2’s PrismCore platform. The open-label, single-arm trial is intended to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of B4t2-001 as a monotherapy for patients with advanced solid tumors including, but not limited to, advanced gastric or gastroesophageal junction adenocarcinoma, advanced pancreatic cancer, advanced non-small cell lung cancer, colorectal cancers, and metastatic breast cancer.
“We are excited to have started the clinical trial for our first CAR-T therapy targeting BT-001, which is a novel antigen for such therapies,” Farzad Haerizadeh, PhD, chief scientific officer and co-founder, Bio4t2, said in a statement regarding the news. “Our CAR-T is calibrated through PrismCore to discriminate between levels of BT-001 on tumors versus healthy cells. Indeed, B4t2-001 in preclinical studies in rodents and non-human primates, safely exhibited potent antitumor activity with long-term protective capacity. This trial helps validate the platform enabling the development of safe and effective CAR-T therapies against multiple types of solid tumors.”
The trial is seeking to recruit approximately 36 patients aged 18 years to 70 years who have locally advanced or metastatic BT-001-positive malignant solid tumors and are unable to receive standard treatment or have disease that is relapsed/refractory to standard treatment. Participants are required to have an Eastern Cooperative Oncology Group score of 0-1, an expected survival of more than 3 months, and measurable or evaluable lesions. Participants must additionally be able to maintain at least 95% oxygen saturation without oxygen inhalation, and have sufficient bone marrow, liver, and kidney functions according to study-specific criteria. Patients who have brain metastases with central nervous system symptoms; patients who previously received other cell therapies or a therapeutic tumor vaccine; patients who previously received any BT-001-targeted therapy; patients with autoimmune disease or a history of immunodeficiency; patients with gastric cancer who have gastric perforation, pyloric obstruction, or complete biliary obstruction; patients with pancreatic cancer who have tumor causing biliary obstruction; patients with severe complications including active gastrointestinal bleeding, intestinal obstruction, intestinal paralysis, interstitial pneumonia, pulmonary fibrosis, renal failure, or uncontrolled diabetes; patients with a history of acute myocardial infarction, unstable angina pectoris, stroke, or transient ischemic attack within 6 months prior to enrollment; and patients with NYHA Class 2 or higher congestive heart failure will be excluded from the study. Additional exclusion criteria relate to patient health status, health history, concurrent treatments, and treatment history.
Participants will be infused with B4t2-001 several days after a lymphodepleting chemotherapy regimen consisting of cyclophosphamide 300mg/m2 once daily and fludarabine 30mg/m2 once daily for 3 consecutive days. The chemotherapy doses may be adjusted as necessary to account for patients’ conditions or comorbidities. The study will follow a dose escalation and dose expansion study design. The study’s primary end points are the incidence of serious adverse events (SAEs) and severity of AEs, as well as the determination of the maximum tolerated dose and the recommended phase 2 dose. Secondary end points include the overall response rate, duration of response, progression free survival, overall survival, and pharmacokinetic measures including the area under curve, maximum concentration, and time to Cmax. Blood cytokine levels, H score, overall immunohistochemistry score, and the percentage of positive stained tumor will also be assessed. The trial is recruiting at 2 hospitals in Shanghai, China, and has an estimated completion date of December 31, 2026.
“This first-in-human study marks the initial therapeutic to be evaluated from Bio4t2’s technology,” Laurence Cooper, MD-PhD, executive chairman of the board, Bio4t2, added to the statement. “PrismCore is capable of rapidly generating CAR-T to safely target self-antigens, opening a new frontier to delivering CAR-T to treat many types of solid tumors. This clinical trial is at the cutting edge of CAR-T biology and provides a path to treating the enormous numbers of patients who suffer from invasive cancers worldwide.”