On June 10, 2021 CBMG Holdings (or the "Company"), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, reported updated clinical data for C-CAR039, a novel CD19/CD20 bi-specific CAR-T cell product in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) (Press release, Cellular Biomedicine Group, JUN 10, 2021, View Source [SID1234583855]). This work was presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, by the Principal Investigator (PI) of the study, Aibin Liang, M.D., Professor of Department of Hematology, Shanghai Tongji Hospital, Tongji University School of Medicine.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Additionally, the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development has granted the Company an orphan drug designation (ODD) to C-CAR039, for the treatment of follicular lymphoma, an indolent form of Non-Hodgkin’s Lymphoma.
"C-CAR039 preliminary data has demonstrated an early favorable safety profile and encouraging efficacy in clinical trial in patients with r/r B-NHL," commented Tony (Bizuo) Liu, Chairman and CEO of CBMG Holdings. "The high response rate, especially the CR rate in r/r DLBCL is likely to allow the asset to differentiate from existing therapies. The clinical efficacy data compares favorably to any existing anti-CD19 CAR-T therapies. We are also pleased that the FDA has recognized C-CAR039’s potential as a treatment option for follicular lymphoma in granting it ODD. This designation speaks to our therapy already showing promise in treating such serious illness and marks another significant regulatory milestone for our C-CAR039 product. We are excited to accelerate the development of C-CAR039 and to bring its potential therapeutic benefits to patients all over the world."
About the Study
C-CAR039 has been developed as a novel 2nd generation 4-1BB bi-specific CAR-T targeting both CD19 and CD20 antigens with an optimized bi-specific antigen binding domain. C-CAR039 can eradicate CD19/CD20 single or double positive tumor cells in vitro and in vivo. GMP manufacturing of C-CAR039 was carried out in a serum free and fully closed semi-automatic system. Dose escalation and expansion studies were conducted to evaluate the safety and efficacy of C-CAR039 in r/r B-NHL patients.
In the Phase I clinical trials in China (NCT04317885, NCT04655677, NCT04696432, NCT04693676), dose escalation and expansion studies were conducted to evaluate the safety and efficacy of C-CAR039 in r/r B-NHL patients. C-CAR039 was administered as a single intravenous dose after a 3-day cyclophosphamide (300mg/m2x3d) plus fludarabine (30mg/m2x3d) conditioning regimen. The median manufacturing time was 6 days and the median vein to vein time was 19 days.
Key Results
As of April 20, 2021, 34 patients were infused with C-CAR039. Among them, 28 (DLBCL, n = 25; PMBCL, n = 1; tFL, n=1; FL, n=1) patients had more than 1 month safety data and 27 were evaluable for efficacy at dose ranges of 1.0 x 106 to 5.0×106 CAR-T cells/kg (1 patient did not have evaluable disease on the day of C-CAR039 infusion). The median age was 55.5 (range, 28-71) years, median number of prior lines of therapy was 3 (range, 1-5), 75% (21/28) of patients were in Ann Arbor Stage III/IV, and 28.6% (8/28) never achieved CR to their prior treatments. 5 patients (17.9%) received bridging therapy.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to ASTCT 2019 criteria. 92.9% (26/28) of patients experienced CRS. 25 of 26 were grade 1 or 2. Only 1 patient experienced grade 3 CRS. All CRS are reversible. 2 patients experienced a grade 1 ICANS. Grade≥3 neutropenia, anemia, thrombocytopenia and infection were reported in 89.3%, 32.1%, 25% and 3.6% of patients, respectively.
At a median follow-up of 7.0 months, the best overall response rate was 92.6% (25/27). The complete response (CR) rate was 85.2% (23/25). Of the 24 DLBCL patients, 20 (83.3%) had complete response. The median time to response was 1.0 month (range, 0.9-1.6). The Kaplan Meyer estimation of PFS at 6 months was 83.2% (95% CI, 69.1 to 100.0). The median duration of response has not been reached.
The Company plans to submit an IND to the US FDA later this year and initiate a Phase 1b study in the first half of 2022 based on communication with FDA.