Tremelimumab

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. 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. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

The Emerald-3 showing draws a resemblance to AstraZeneca’s Emerald-1 readout in the same locoregional treatment setting among liver cancer patients eligible for TACE. Another green light appears increasingly within reach for AstraZeneca’s Emerald program after a combo regimen featuring the company’s immunotherapy duo, Imfinzi and Imjudo, showed benefit in certain liver cancer patients. Results from the phase 3 Emerald-3 trial showed that the combination, paired with transarterial chemoembolizaton (TACE) and Lenvima, significantly improved progression-free survival (PFS) versus TACE alone in patients with unresectable locoregional hepatocellular carcinoma. Lenvima is a multikinase inhibitor sold by Merck & Co. and Eisai.But whether AZ has struck gold with Emerald-3 remains to be seen. Overall survival (OS), a secondary endpoint that will be a key consideration for the FDA, was immature at the interim analysis, although AZ highlighted a trend toward improvement in its April 2 announcement. In two ways, the Emerald-3 showing draws a resemblance to AZ’s Emerald-1 readout in the same locoregional treatment setting among liver cancer patients eligible for TACE. Two years ago, the Emerald-1 trial hit its primary endpoint, showing that a cocktail of Imfinzi, Avastin and TACE reduced the risk of progression or death by 23% versus TACE alone. At that time, OS was also immature, and AZ’s oncology R&D chief, Susan Galbraith, Ph.D., flagged that patient survival data are crucial in this locoregional setting. Case in point: Despite a PFS win, Merck & Co. last year abandoned hopes for a similar liver cancer approval for its Keytruda-Lenvima-TACE regimen after it failed to improve OS compared with TACE alone.Emerald-1 still hasn’t reported its final OS data, and the study has not graduated to the regulatory submission batch in AZ’s most recent earnings report in February.  In addition, like Emerald-1, Emerald-3 has a second experimental arm. In this cohort, Imfinzi, Imjudo and TACE—without Lenvima—showed what AZ called “strong trends” toward improved PFS and OS, although these analyses were not formally tested. Previously, in Emerald-1, only the Avastin-containing triplet beat TACE, while Imfinzi-TACE failed to move the needle. AZ is discussing the latest Emerald-3 data with global regulatory authorities while waiting for final results from the trial’s key secondary endpoints, Galbraith said in an April 2 statement.As for Emerald-1, an AZ spokesperson said the company will share additional data in the future and will update its regulatory discussion plans as appropriate. Liver cancer helped AZ’s CTLA-4 agent Imjudo break into the market in 2022 as part of a combination with Imfinzi in unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer. Patients who are eligible for embolization have an earlier stage of disease. In 2026, more than 200,000 patients belong to this category, according to data cited by AZ—however, most patients who receive the procedure experience progression or recurrence within six to ten months.The British pharma also has a third Emerald. Called Emerald-2, the phase 3 study is testing Imfinzi with Avastin in adjuvant liver cancer, with its data expected in the second half of 2026. As for the Imfinzi-Imjudo duo, AZ also expects readouts this year from its Nile trial in first-line metastatic bladder cancer and from its Volga study assessing a neoadjuvant regimen in cisplatin-ineligible muscle-invasive bladder cancer. Both will need to live up to the high expectations set by the combination of Merck & Co.’s Keytruda and Pfizer and Astellas’ antibody-drug conjugate Padcev.For AZ’s broader oncology portfolio, the company is bracing for an upcoming FDA advisory committee meeting that will dig into two separate applications for its oral SERD med camizestrant and the AKT inhibitor Truqap. The high-stakes first-line non-small cell lung cancer readout for Daiichi Sankyo-partnered Datroway from the Avanzar trial is also expected this year.