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According to abstracts from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Cybio will present the latest clinical research data for two novel CAR-T therapies during the event. One is a bispecific CAR-T therapy targeting CD20 and CD19, while the other is a second-generation CAR-T therapy targeting CD20.Preliminary data suggest these potential best-in-class novel CAR-T therapies may offer new hope for patients with relapsed/refractory B-cell non-Hodgkin lymphoma.
Drug Name: C-CAR039
Mechanism of Action: CD20×CD19 Bispecific CAR-T Therapy
Indications: Relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL)
C-CAR039 is an innovative bispecific CAR-T therapy featuring an optimized bispecific antigen-binding domain that simultaneously targets CD19 and CD20 antigens.In both in vivo and in vitro studies, C-CAR039 demonstrated efficacy against CD19-positive and/or CD20-positive tumor cells. Results from a dose-escalation and expansion study evaluating the safety and efficacy of C-CAR039 in patients with relapsed/refractory B-NHL will be presented at this conference.The dosing regimen consisted of a single intravenous infusion of C-CAR039 following a 3-day induction regimen of cyclophosphamide plus fludarabine.
As of January 31, 2021, 28 patients received infusion treatment, with 25 evaluable patients. Among them, 22 patients had diffuse large B-cell lymphoma (DLBCL), and 1 patient each had primary mediastinal large B-cell lymphoma (PMBCL), follicular lymphoma (FL), and transformed follicular lymphoma (tFL).The median age of patients was 54 years, with a median of 3 prior lines of therapy. Seventy-six percent of patients had Ann Arbor Stage III/IV disease, and 80% were refractory to last-line therapy. Five patients received bridging therapy.
Data showed: Among evaluable patients, the best overall response rate was 92%, with a complete response (CR) rate of 84% and a median time to response of 1.0 month. At a median follow-up of 5.3 months, 76% of patients remained in complete remission; the estimated 6-month progression-free survival (PFS) rate was 87.3%.Median duration of response was not yet reached. Additionally, C-CAR039 demonstrated favorable cell kinetic characteristics.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were evaluated according to the ASTCT 2019 criteria. The study showed: Among 25 patients, 24 experienced CRS, with 23 cases graded as Grade 1 or 2 and 1 case as Grade 3;The median time to CRS onset was 3 days, with a median duration of 4 days. ICANS occurred in 2 patients, both Grade 1. The incidence rates of ≥Grade 3 neutropenia, anemia, thrombocytopenia, and infection were 88%, 40%, 16%, and 0%, respectively.
The study concluded that in this early-phase clinical trial, C-CAR039 demonstrated favorable safety and encouraging clinical efficacy in patients with relapsed/refractory B-NHL. Xibiman Biotech will evaluate these findings in a larger cohort of follow-up patients to determine the safety, efficacy, and duration of response for C-CAR039.
Drug Name: C-CAR066
Mechanism of Action: CD20-targeted CAR-T therapy
Indications: Relapsed/refractory B-cell non-Hodgkin lymphoma
It is well-known that relapse due to CD19 antigen loss poses a challenge for CD19-targeted CAR-T therapies.These patients generally have poor prognosis and represent a high unmet medical need. CD20 is an effective therapeutic target for B-NHL, validated in clinical trials. C-CAR066 is a novel second-generation CAR-T therapy targeting the CD20 antigen, developed by Xibiman Bio. Preclinical studies demonstrate that C-CAR066 exhibits strong antitumor activity.
This conference will present a Phase 1 clinical trial evaluating the safety and efficacy of C-CAR066 in patients with relapsed/refractory B-NHL who have previously received CD19-targeted CAR-T therapy.The administration regimen consists of a single infusion of C-CAR066 following a 3-day lymphodepletion regimen of cyclophosphamide plus fludarabine, with bridging therapy permitted.As of January 31, 2021, seven patients were enrolled: six with diffuse large B-cell lymphoma (DLBCL) and one with transformed follicular lymphoma (tFL). The median number of prior lines of therapy was five. One patient had undergone autologous stem cell transplantation, and one received bridging therapy.
Data showed: At a median follow-up of 7.8 months, the best overall response rate was 100%, with 71.4% achieving complete remission; median time to response was 1.0 month, and median time to complete remission was 2.7 months; by the cutoff date, 3 patients (2 PR, 1 CR) experienced disease progression; median duration of response was not yet reached.
Regarding adverse events: All 7 patients developed CRS, predominantly Grade 1 or 2; one patient experienced Grade 4 CRS, which resolved after treatment with tocilizumab and corticosteroids. Median time to CRS onset was 5 days, with a median duration of 4 days. No ICANS was observed;Grade 3 incidence rates for neutropenia, anemia, thrombocytopenia, and infection were 57.1%, 42.9%, 28.6%, and 14.3%, respectively.
The study concluded that C-CAR066 demonstrated favorable safety and promising efficacy in patients with relapsed/refractory B-NHL following failure of CD19-targeted CAR-T therapy.These findings suggest that C-CAR066 possesses a distinct mechanism of action compared to CD19-targeted CAR-T therapies, offering a potential new treatment option for B-NHL patients who have failed CD19-targeted CAR-T therapy.