AZD7003 / AbelZeta Pharma, Zhejiang University, AstraZeneca - LARVOL DELTA

Phase I study of C-CAR031, a GPC3-targeted TGFβRIIDN armored autologous CAR-T, in advanced hepatocellular carcinoma (aHCC): Updated Results (ESMO 2026) - No abstract available

CAR T-Cell Therapy • Metastases • P1 data • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3 • TGFB1

GPC3-specific dnTGFβRII-armoured CAR T cells for hepatocellular carcinoma. (PubMed, Nature) - P1 | "High-throughput analyses of tumour samples and functional validation suggested that GPC3 antigen loss and increased TGFβ levels may contribute to C-CAR031 resistance. Collectively, these results indicate that C-CAR031 has a manageable safety profile and encouraging antitumour activity in heavily pretreated patients with advanced HCC."

First-in-human • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3 • TGFB1

Phase I study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR-T, in patients with advanced hepatocellular carcinoma (HCC). (ASCO 2024) - P1 | "The study showed a manageable safety profile and encouraging anti-tumor activity of C-CAR031 in heavily treated advanced HCC patients."

Clinical • Metastases • P1 data • Gastrointestinal Cancer • Hematological Disorders • Hepatocellular Cancer • Interstitial Lung Disease • Neutropenia • Oncology • Pneumonia • Solid Tumor • Thrombocytopenia • GPC3 • TGFB1

An Phase I Trial of a CAR T-cell Infusion C-CAR031 in Participants With GPC3+ Advanced/Metastatic Squamous Cell Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Shanghai AbelZeta Ltd.

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GPC3

AbelZeta Pharma…announced that AstraZeneca has agreed to acquire AbelZeta's 50% share of the China development and commercialization rights to C-CAR031, such that AstraZeneca acquires the sole right to develop, manufacture and commercialize C-CAR031 globally (PRNewswire) - "Under the terms of the agreement, AbelZeta will be entitled to receive up to $630 million from AstraZeneca including an upfront payment, and development, regulatory and sales milestone payments for the GPC3 program in China. Under the terms of a prior agreement with AbelZeta, AstraZeneca owns the development, manufacturing and commercialization rights to C-CAR031 in rest of world, outside of China. AbelZeta is also eligible to receive additional milestone payments and royalties for rest of world development."

Licensing / partnership • Hepatocellular Cancer

A Study to Evaluate Safety and Efficacy of Armored CAR-T Cell Injection C-CAR031 in Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Zhejiang University | N=44 ➔ 72

Enrollment change • Breast Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

A Study to Evaluate C-CAR031 in Glypican-3 (GPC3)+ Advanced/Recurrent Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P1/2 | N=121 | Recruiting | Sponsor: Shanghai AbelZeta Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Oncology • Solid Tumor

A Study to Evaluate C-CAR031 in Glypican-3 (GPC3)+ Advanced/recurrent Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P1/2 | N=121 | Not yet recruiting | Sponsor: Shanghai AbelZeta Ltd.

Metastases • New P1/2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Phase 1 trial of C-CAR031 (CAR-T) in advanced #HCC Very interesting and provocative data. Need to validate but nice work!! @asco #ABS 4020 @asco #ASCO24 #cancer #cancerresearch @AHPBA

ATHENA: A phase 1/2 study of AZD5851, a chimeric antigen receptor (CAR) T-cell therapy directed against GPC3 in adult patients with advanced/recurrent hepatocellular carcinoma (HCC). (ASCO 2024) - P1/2 | "Early clinical data with C-CAR031, a CAR-T product with the same GPC3-specific CAR and dnTGFβRII-armoring transgene as AZD5851, showed promising tolerability and antitumor activity in pts with HCC [1]. AACR 2023. Abstract CT097."

Clinical • IO biomarker • Metastases • P1/2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

AbelZeta announces clinical data showing preliminary anti-tumor activity for C-CAR031, an armored autologous GPC3 CAR-T, in patients with advanced hepatocellular carcinoma, at ASCO Annual Meeting 2024 (PRNewswire) - P1 | N=44 | NCT05155189 | "AbelZeta Pharma, Inc...announced preliminary safety and efficacy results from its first time in human investigator-initiated trial (IIT) of C-CAR031 in connection with the Company's oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....Tumor reductions were observed in 91.3% patients, in both intrahepatic and extrahepatic lesions, with a median reduction of 42.2% (range, -28.1% 94.4%). The disease control rate was 91.3% and the ORR was 56.5% for patients across all DLs. In DL4, the ORR was 75.0%. With 9.03-month median follow-up, Kaplan-Meier estimation of median overall survival (mOS) is 11.14 months (95% CI, 7.56-NE)."

P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

AbelZeta Announces Publication of Abstract for ASCO 2024 Annual Meeting (PRNewswire) - "AbelZeta Pharma, Inc...announced that data from its C-CAR031 study has been published in an abstract available on the 2024 American Society of Clinical Oncology's (ASCO) official website, in connection with the Company's oral presentation at the ASCO Annual Meeting taking place in Chicago May 31 to June 4, 2024. The presentation will share safety and preliminary efficacy data for C-CAR031 across 24 patients with hepatocellular carcinoma (HCC)."

P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

AbelZeta Announces Abstract for C-CAR031 Accepted for Presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - "AbelZeta Pharma...today announced the acceptance of an abstract related to the clinical study of C-CAR031, an autologous, armored GPC3-targeting chimeric antigen receptor T-Cell (CAR-T) therapy, in hepatocellular carcinoma (HCC) for oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago May 31 to June 4, 2024."

P1 data • Hepatocellular Cancer • Liver Cancer

A Study to Evaluate Safety and Efficacy of Armored CAR-T Cell Injection C-CAR031 in Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Zhejiang University | N=20 ➔ 48

Enrollment change • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3

AbelZeta Pharma Announces Agreement with AstraZeneca to Co-Develop a novel Glypican 3 (GPC3) Armored CAR-T Therapy in China (PRNewswire) - "AbelZeta Pharma Inc...announced an agreement with AstraZeneca to co-develop C-CAR031, an autologous, armored GPC3-targeting chimeric antigen receptor T Cells (CAR-T) therapy, in hepatocellular carcinoma...Under the terms of the agreement, AbelZeta will receive an upfront payment from AstraZeneca for the co-development and commercialization of C-CAR031 in China. AbelZeta is also eligible to receive milestone payments and royalties for the global development of AZD5851, which is being solely developed, manufactured and commercialized by AstraZeneca outside of China. "

Licensing / partnership • Hepatocellular Cancer

"Here's the corrected C-CAR031 waterfall $AZN #AACR23" (,@JacobPlieth)

Oncology

"Aha, here's the Chinese connection for $AZN C-CAR031:" (,@JacobPlieth)

"Summary of $AZN Car-T projects AZD0754 (preclinical) & C-CAR031 (FIH). These were the posters #AACR23 didn't make available to virtual attendees." (,@JacobPlieth)

Preclinical • Oncology

First report of preliminary safety, efficacy, and pharmacokinetics of C-CAR031 (GPC3-specific TGFβRIIDN CAR-T) in patients with advanced HCC (AACR 2023) - "In this FIH study, C-CAR031 is well tolerated and shows promising anti- tumor activity. Enrollment is ongoing to confirm initial results."

Clinical • IO biomarker • Metastases • PK/PD data • Hepatocellular Cancer • Oncology • GPC3 • TGFB1

Shanghai Cellular Biopharmaceutical Group presents first data from Phase I trial evaluating a novel CAR-T in advanced liver cancer at AACR Annual Meeting (PRNewswire) - P1 | N=20 | NCT05155189 | "Shanghai Cellular Biopharmaceutical Group Ltd...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....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."

P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

AstraZeneca advances its pipeline and highlights progress in immuno-oncology, ADCs, cell therapy and epigenetics at AACR (AstraZeneca Press Release) - "In cell therapy, the first clinical data will be presented for C-CAR031, a novel transforming growth factor-beta (TGFβ) armoured Glypican 3 (GPC3) targeting chimeric antigen receptor T cell (CAR-T) therapy that is being investigated for liver cancer. Early results show it is well tolerated with promising anti-tumour activity seen with objective responses in several patients to date....In addition, the first preclinical data will be shared on AZD0754, a novel TGFβ armoured CAR-T targeting STEAP2, a protein commonly overexpressed in prostate cancer."

Clinical data • Preclinical • Gastrointestinal Cancer • Genito-urinary Cancer • Liver Cancer • Oncology • Prostate Cancer • Solid Tumor