On April 17, 2023 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, reported data from the First-in-Human (FIH) Phase I trial evaluating C-CAR031 at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Cellular Biomedicine Group, APR 17, 2023, View Source [SID1234630198]).

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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.

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:

View Source!/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.