ASCO24: AstraZeneca's armoured CAR-T shrinks liver tumours

03 Jun 2024
firstwordpharma.com
Phase 1Cell TherapyASCOImmunotherapyClinical Result
Researchers unveiled some promising early clinical data on AstraZeneca's next-generation autologous CAR-T cell therapy C-CAR031, showing the experimental treatment could substantially reduce tumour burden in patients with advanced hepatocellular carcinoma (HCC).
C-CAR031 targets the GPC3 surface antigen, which is highly expressed in HCC, but largely absent from normal tissue. The "armoured" CAR-T construct was engineered to resist immunosuppressive signals like TGF-beta in the solid tumour microenvironment. AstraZeneca is partnered on the treatment with AbelZeta, which manufactures C-CAR031 in China.
The Phase I data from 22 efficacy evaluable patients, presented at the American Society of Clinical Oncology (ASCO) annual meeting on Monday, demonstrated an overall response rate of 50% across all dose levels in the Phase I dose-escalation study, including 11 partial responses (PRs) and 1 unconfirmed PR, according to an abstract of the study. At the highest dose level evaluated, 57.1% of patients achieved an objective response, including 4 PRs and 1 unconfirmed PR.
The 24 patients enrolled had GPC3+ advanced HCCGPC3+ advanced HCC that progressed after receiving at least one and a median of 3.5 prior lines of therapy, including immune checkpoint inhibitors and tyrosine kinase inhibitors in nearly all cases.
Researchers noted that over four-fifths of patients had extrahepatic metastases at baseline. They noted that tumour reductions were observed in 90.9% of patients, "not only in intrahepatic lesions, but also extrahepatic ones with a median reduction of 44%."
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