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Grand Pharma's SIR-Spheres Y-90 aces endpoints in HCC Phase III

Grand Pharmaceutical Group (HKEX: 00512) announced that the DOORwaY90 trial of SIR-Spheres Y-90 resin microsphere injection in unresectable hepatocellular carcinoma met its prespecified co-primary endpoints, completing a study whose interim data had already secured FDA approval for the HCC indication.

The DOORwaY90 study is a pivotal, prospective, multicenter trial of Y-90 selective internal radiation therapy using partition dosimetry in patients with unresectable HCC in the United States — the first such registrational study in this setting. The trial was conducted through Sirtex Medical Pty Ltd, an associate company of Grand Pharma.

By blinded independent central review, the study achieved a complete response rate of 90% and a best overall response rate of 99%. All evaluable patients responded to treatment, yielding 100% local tumor control. Responses were durable: 75% lasted beyond six months, with a median duration of 295 days. Over 95% of patients maintained stable liver function at 12 months, a finding the company characterized as evidence that personalized dosimetry preserves hepatic reserve.

No detailed safety data were disclosed in the announcement beyond the liver function finding.

SIR-Spheres Y-90 resin microspheres work by delivering yttrium-90 via intra-arterial injection into hepatic tumor vasculature, where beta radiation causes localized tumor cell death without a discrete molecular target. The product has been commercially available since 2002 for colorectal cancer liver metastases and now carries FDA approval for unresectable HCC — the only selective internal radiotherapy product approved for both indications. Its most direct competitor in the SIRT category is TheraSphere, Boston Scientific's glass microsphere platform, which received FDA approval for HCC in 2021. The two products share the same delivery modality and radionuclide but differ in microsphere composition and dosimetry methodology; DOORwaY90 used a partition dosimetry model, while the pivotal evidence base for TheraSphere relied substantially on the retrospective LEGACY study. Cross-trial comparisons are limited by differences in patient selection, dosimetry protocols, and endpoint definitions.

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The broader HCC treatment landscape is dominated by systemic agents — atezolizumab plus bevacizumab, the STRIDE regimen of tremelimumab and durvalumab, and most recently nivolumab plus ipilimumab, which gained first-line approval in April 2025 based on the CheckMate 9DW trial. These combinations achieve overall response rates in the range of 13–36% by conventional criteria. The DOORwaY90 response figures are not directly comparable to those systemic trials, which enrolled different patient populations and used survival rather than response as primary endpoints. What the DOORwaY90 data does establish is a prospective, blinded evidentiary basis for locoregional radioembolization in a population where liver function preservation is a clinical priority — a dimension that systemic checkpoint inhibitor combinations do not directly address.

Grand Pharma indicated the full dataset will support a regulatory filing strategy in China, where the NMPA approved a Phase II registrational trial for the HCC indication in May 2025. The company holds a dual US-China filing strategy for the product and received CE Mark approval in Europe for multiple liver cancer indications in August 2025.

The next anticipated milestone is publication of the complete DOORwaY90 dataset and its application to the Chinese regulatory pathway.


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