Promising anti-tumor activity reported for C-CAR031, a novel Glypican 3 (GPC3)-targeting cell therapy designed by AstraZeneca

SHANGHAI, China I April 17, 2023 I Shanghai Cellular Biopharmaceutical Group Ltd. (the Company, or Shanghai Cellular Bio), a company engaged in the drug development of immunotherapies for cancer and stem cell therapies for degenerative diseases, today presented data from the First-in-Human (FIH) Phase I trial evaluating C-CAR031 at the 2023 American Association for Cancer Research (AACR) Annual Meeting.

Early results indicate that C-CAR031 is well tolerated with promising anti-tumor activity seen and objective responses in several patients to date, including 3 patients with confirmed partial responses, 2 with stable disease and 1 with progressive disease per both RECIST v1.1 and mRECIST criteria. The clinical responses of the patients who achieved partial responses are ongoing up to the data cutoff date.

Early results indicate that C-CAR031 is well tolerated with promising anti-tumor activity

C-CAR031 is an autologous GPC3-directed second generation armored CAR-T with affinity-tuned single-chain variable fragment (scFv) to enhance its  safety profile, based on a novel cell therapy designed by AstraZeneca (LSE/STO/Nasdaq:AZN) using their TGFβRII dominant negative armoring discovery platform.

To investigate the feasibility, safety and initial efficacy of C-CAR301 in hepatocellular carcinoma (HCC), Shanghai Cellular Bio is currently conducting a Phase I FIH clinical study (NCT05155189) in advanced HCC in The First Affiliated Hospital, Zhejiang University School of Medicine in Hangzhou, China.

Poster Title: First report of preliminary safety, efficacy, and pharmacokinetics of C-CAR031 (GPC3-specific TGFβRIIDN CAR-T) in patients with advanced HCC”
Session:            Session PO.CT01.01 – First-in-Human Phase I Clinical Trials 1
Poster No:         CT097
Date:               Monday, April 17, 2023
Time:               1:30 pm to 5:00 p.m. EDT
Location:         Orange County Convention Center in Orlando, Florida
  Exhibit Halls Poster Section 45, Poster Board Number 5
Website: !/10828/presentation/10293

Methods: This FIH, open-label dose escalation trial employs an accelerated dose titration plus i3+3 design. Histologically confirmed GPC3+ advanced HCC patients (pts) who failed systemic treatments received a single-dose i.v. infusion of C-CAR031 following standard lymphodepletion. The primary objective was to assess the safety and tolerability. Adverse events (AEs) were graded using CTCAE 5.0, and cytokine release syndrome (CRS) / immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to ASTCT 2019 criteria.

Results: As of March 2nd, 2023, seven patients received two dose levels (DL1, n=1; DL2, n=6) of C-CAR031. The median number of prior lines of therapies was 4 (range 1-6). The median follow-up was 77 (67-213) days. Seven patients with ≥28 days’ follow-up were eligible for safety evaluation. Good safety profile was observed at explored dose levels.  86% (6/7) patients experienced Gr1/2 CRS; no Dose Limiting Toxicities (DLT) or ICANS was observed. The ≥Gr3 non-hematologic product-related AE included transient Gr3 AST elevation (2/7, 28%), hypokalemia (1/7, 14%), and abdominal pain (1/7,14%). 5/6 (83%) patients at DL2 showed tumor shrinkage post C-CAR031 treatment (median -41.4% range -3.4%~ – 94.4%).  Best clinical responses at DL2 included 3 confirmed PR, 2 SD and 1 PD per both RECIST v1.1 and mRECIST. The clinical responses of the patients who achieved PR are ongoing up to the cutoff date. C-CAR031 showed a robust cellular kinetic profile. CAR-T cells were detectable in blood of all patients in the last follow-up.

Conclusion: In this FIH study, C-CAR031 is well tolerated and shows promising anti-tumor activity. Enrollment is ongoing to confirm initial results.

About Shanghai Cellular Biopharmaceutical Group Ltd

Shanghai Cellular Biopharmaceutical Group Ltd develops proprietary cell therapies for the treatment of cancerous diseases and autoimmune diseases, and operates state-of-the-art research and GMP facility in Shanghai, China.   Shanghai Cellular Bio partners with its affiliate in Maryland to augment its global research and development capabilities. Shanghai Cellular Bio and its affiliate conduct multiple clinical studies comprised of C-CAR039 Phase 1b trial, C-CAR066  targeting treatment for r/r NHL, C-CAR088, an autologous anti-B cell maturation antigen (BCMA) CAR-T for r/r myeloma (MM), C-CAR031, an autologous armored anti-GPC3 CAR-T for Hepatocellular carcinoma (HCC), C-TIL051, an autologous tumor-infiltrating lymphocytes (TIL) therapy for non-small cell lung cancer (NSCLC);  and continue to discover and develop multiple novel T cell therapies for solid tumor and for orphan autoimmune diseases.

SOURCE: Shanghai Cellular Biopharmaceutical Group