Enfortumab Vedotin-ejfv

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. 

Astellas Pharma (Japan) has terminated its Phase I clinical trial of ASP5502, an oral small-molecule STING (Stimulator of Interferon Genes) inhibitor, in healthy adults and patients with primary Sjögren’s syndrome. The clinical trial terminated before completion, according to an updated record on ClinicalTrials.gov (NCT06544642), with the status verified as of March 2026. The study, which began enrolling participants in August 2024 at a Fortrea Clinical Research Unit in Daytona Beach, Florida, had been designed as a first-in-human evaluation of the compound. No results have been posted to the registry. The study was a randomized, double-masked, placebo-controlled Phase I trial with a three-part design: single ascending doses (including a food-effect cohort), multiple ascending doses in healthy volunteers over 14 days, and a 28-day repeated-dose cohort in adults with primary Sjögren’s syndrome without a placebo comparator. The trial planned to enroll 116 participants aged 18–65, with primary endpoints focused on safety and tolerability (adverse events, laboratory abnormalities, vital signs, and ECGs) and secondary endpoints assessing pharmacokinetics and cardiac safety. The Sjögren’s cohort required a diagnosis based on 2016 ACR-EULAR criteria and excluded patients receiving immunosuppressive or B-cell–targeting therapies or with other systemic autoimmune conditions. Termination context The study was terminated for strategic reasons, according to the ClinicalTrials.gov NCT06544642 entry, with no indication of safety concerns or lack of efficacy. The decision comes amid Astellas’ broader efforts to prioritize late-stage and core therapeutic areas, although the company has not publicly linked those changes to ASP5502 specifically. ASP5502 was positioned within Astellas’s immune homeostasis research area, which sits outside the company’s four declared primary focus areas: immuno-oncology, targeted protein degradation, genetic regulation, and blindness and regeneration. Astellas has been executing a systematic drug development pipeline update over the past two years, driven in large part by the approaching patent cliff for enzalutamide (Xtandi), its largest revenue-generating product, with generic competition expected around 2027. The company has concentrated resources on late-stage oncology assets — enfortumab vedotin (Padcev), zolbetuximab (Vyloy), and several degrader and antibody-drug conjugate programs — while pruning early-stage assets in non-core therapeutic areas. Prior discontinuations include a CAR-T program derived from the Xyphos acquisition and a KRAS G12D pancreatic cancer program (ASP4396), with the company recording approximately JPY 12.8 billion in discontinuation-related losses. A February 2025 management restructuring created a new Chief R&D Officer role consolidating oversight of research and development divisions, a move interpreted as tightening portfolio governance. AllSci lists no other active clinical trials for ASP5502, although Astellas has not confirmed the molecule’s discontinuation publicly. The Sjögren’s syndrome landscape Primary Sjögren’s syndrome affects an estimated 0.5% to 1.0% of the adult population, predominantly women, and is characterized by lymphocytic infiltration of exocrine glands leading to sicca symptoms — dry eyes and dry mouth — along with systemic manifestations including fatigue, arthralgia, and organ involvement. Despite its prevalence and burden, no therapy has received FDA approval specifically for the treatment of primary Sjögren’s syndrome. Current management relies on symptomatic relief and off-label use of immunosuppressants. The therapeutic landscape has seen repeated clinical failures. Bristol Myers Squibb’s abatacept did not meet its primary endpoint in a Phase III trial. Novartis tested ianalumab (an anti-BAFF receptor antibody) and reported mixed results, though development continues. GSK’s belimumab, approved for lupus, has been explored in Sjögren’s syndrome without regulatory success in that indication. Horizon Therapeutics (now Amgen) evaluated teprotumumab but in a different autoimmune context. The BAFF/APRIL axis, B-cell depletion, and T-cell co-stimulation blockade have all been pursued with limited translational success in this disease. STING inhibition represented a mechanistically distinct approach. The STING pathway, part of the innate immune system’s cytosolic DNA sensing machinery, has been implicated in the pathogenesis of several autoimmune conditions, including Sjögren’s syndrome, where aberrant type I interferon signaling is a recognized feature. Preclinical rationale for targeting STING in Sjögren’s syndrome rests on the observation that chronic activation of the interferon pathway contributes to glandular inflammation and tissue damage. However, translating STING pathway modulation into clinical benefit in autoimmune disease remains unproven, and ASP5502 was among the first oral STING inhibitors to enter human testing for this indication. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website