The CR was achieved at 1-month post-treatment.
PeproMene Bio’s PMB-CT01 (BAFFR-CAR T Cells), an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy being evaluated for the treatment of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) in a phase 1 clinical trial (NCT05370430), produced a complete response (CR) in the first patient treated.
PMB-CT01 is intended to target B-cell activating factor receptor (BAFF-R). Because research suggests that BAFF-R is required for B-cell survival, the company expects that cancer cells will not be able to evade the therapy by loss of the antigen. In previous preclinical research, PMB-CT01 demonstrated the ability to kill human lymphomas and leukemias in vitro and in animal models.
The clinical trial is taking place at City of Hope Medical Center, which licensed intellectual property relating to the therapy to PeproMene Bio. The above-mentioned patient achieved the CR at 1 month after treatment. In terms of safety, it was noted that the patient experienced low grade treatment-emergent toxicities during the first month. This included a grade 1 case of cytokine release syndrome from which the patient fully recovered. No incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was observed.
“This mantle cell lymphoma patient has been refractory to several prior lines of treatment including chemoimmunotherapy, BTK inhibitor, Venetoclax, and CD19-CAR T therapy,” Elizabeth Budde, MD, PhD, City of Hope associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, and the principal investigator of the trial, said in a statement. “We are pleased to see a deep complete remission which is minimal residual disease (MRD) negative.”
The single-center, open-label, dose escalation trial will aim to enroll approximately 18 participants aged 18 years or older with histologically confirmed mantle cell lymphoma (MCL) with evidence of positive BAFF-R expression on the MCL cells. Patients with another r/r BAFFR+ B-cell lymphoma with no standard of care options will be allowed to enroll in the initial dose escalation phase, but not in the dose expansion phase. All participants are required to have an Eastern Cooperative Oncology Group score of 2 or lower. Participants must have r/r disease after at least 1 prior therapeutic regimen according to specific criteria. Patients with newly-diagnosed MCL who do not have standard of care options may also be eligible at the discretion of the principal investigator. Participants are additionally required to have measurable disease by CT scan or evidence of blood, gastrointestinal, skin, bone marrow, or spleen involvement; must have fully recovered to grade 1 or lower from all acute toxic effects of prior anti-cancer therapy, excepting alopecia; must have a total bilirubin less than or equal to 1.5 x the upper limit of normal (ULN) or, if the patient has Gilbert disease, at least 3.0 x ULN with direct bilirubin less than or equal to 1.5 x ULN; must have aspartate aminotransferase and alanine transaminase levels less than 3 x ULN; must have a creatinine clearance of at least 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula; must have a left ventricular ejection fraction of at least 45%, a QTc of less than or equal to 480 ms, an O2 saturation of more than 91% on room air; and must be seronegative for HIV Ag/Ab combo, HCV, active HBV (Surface Antigen Negative). Patients who have received prior CAR-T therapy are allowed to participate if 90 days have passed by the time of leukapheresis.
Patients who previously received allogeneic stem cell transplant, those who received autologous stem cell transplant within 90 days of enrollment, those with concurrent use of systemic steroids or chronic use of immunosuppressant medications, patients with cardiac lymphoma involvement, patients who require urgent therapy due to tumor mass effects, and patients with active central nervous system (CNS) MCL or a history of CNS MCL within 3 months prior to screening will be excluded from participation in the study. Additional exclusion criteria relate to patient health status, health history, and treatment history. Patients who currently use inhaled steroids will not be excluded, and physiologic replacement of steroids will be allowed. Systemic corticosteroids may be administered during the trial to address treatment-emergent adverse events.
The trial’s primary end points are the incidence of adverse events and the determination of the maximum tolerated dose. Secondary end points include disease response, incidence of negative MRD, a B-cell quantification measured by flow cytometry, progression-free survival, and overall survival. The trial has an estimated completion date of June 13, 2026. PMB-CT01 is also currently being investigated in a separate phase 1 clinical trial (NCT04690595) for patients with r/r B-cell acute lymphoblastic leukemia.
“Despite high initial efficacy of CD19-CAR T-cell treatment for B-cell lymphoma and leukemia, there is a significant unmet medical need for those patients who unfortunately relapse,” Larry W. Kwak, MD, PhD, vice president and deputy director of City of Hope’s Comprehensive Cancer Center and PeproMene’s scientific founder and compensated chair of the company's Scientific Advisory Board, added to the statement. “As BAFF-R is a novel tumor target for B-cell malignancies, I am hoping BAFFR-CAR T therapy will offer a clinically meaningful, new option for those patients.”