お知らせ • Jul 28
Lantern Pharma Advances EMA-Cleared Phase 1b/2 Trial Of LP-184 (Zirdafulven) In Biomarker-Selected Advanced Bladder Cancer
Lantern Pharma Inc. announced that an investigator-initiated Phase 1b/2 clinical trial of its lead drug candidate LP-184 (zirdafulven) in advanced, recurrent bladder cancer has been cleared by the European Medicines Agency (EMA). The study will be conducted at Rigshospitalet in Copenhagen in collaboration with Professor Helle Pappot, MD, DMSc. The trial is designed to test a novel, biomarker-guided approach in patients with advanced or metastatic urothelial carcinoma who have progressed on or are ineligible for current standard-of-care regimens. It is among the first studies to prospectively select patients using a dual biomarker strategy—combining overexpression of the activating enzyme PTGR1 with tumor DNA-damage-repair (DDR) deficiency—to match the mechanisms of LP-184 to the tumors believed most likely to respond. No FDA approved therapy for Nucleotide Excision Repair Deficient (NERD) tumors exists. The company estimates that approximately 20% to 25% of bladder cancer cases progress to a need for therapy in the third line representing 130,000+ patients globally and a potential market opportunity of USD 3,000 million by 2035. The trial is an investigator-initiated, open-label Phase 1b/2 study. The study site is Rigshospitalet, Copenhagen, Denmark. Clinical Investigators are Prof. Kristoffer Staal Rohrberg, MD, PhD - Sponsor & Principal Investigator and Prof. Helle Pappot, MD, DMSc – Coordinating Investigator. The indication is advanced /metastatic urothelial carcinoma (bladder cancer). The line of therapy is relapsed /refractory after standard of care (= 2nd line; includes patients treated after enfortumab vedotin + pembrolizumab). Patient selection is dual biomarker—PTGR1 overexpression + DNA-damage-repair (NER /HR) deficiency. The route & schedule is IV, administered on Days 1 and 8 of each 21-day cycle. The primary endpoint is objective response rate (ORR) by RECIST 1.1. Planned enrollment is up to approximately 39 patients. Regulatory status is cleared by the European Medicines Agency (EMA). Bladder cancer is a top-ten global cancer (~550,000 new cases per year; ~84,500 in the U.S. in 2026; ~2,000 per year in Denmark, up to 20% metastatic or unresectable at diagnosis). Options after first-line therapy are limited and non-standardized; the global metastatic urothelial carcinoma market is projected to grow from ~USD 3,700 million (2025) to ~USD 12,800 million by 2035. The development opportunity for LP-184 is initially aimed at the third-line setting—reached by ~25% of patients—representing an estimated ~137,500 eligible patients globally per year, with the majority of the commercial opportunity concentrated in the United States, Europe, and Japan. Bladder cancer is among the ten most common cancers worldwide, with approximately 550,000 new cases diagnosed each year—including an estimated 84,500 in the United States in 2026. In Denmark, roughly 2,000 patients are diagnosed with bladder tumors annually, and up to 20% present with metastatic or unresectable disease. Following the adoption of enfortumab vedotin plus pembrolizumab as a first-line standard of care for advanced urothelial cancer, patients who progress have few effective options and generally modest outcomes, with no clearly established standard for later lines of therapy. The scale of that gap was quantified in the recently published multicenter STATES-Bladder real-world study (Urologic Oncology, 2026), which followed 180 patients with metastatic urothelial cancer treated in routine practice across four centers in France. Despite a median overall survival of 22.4 months, the study documented sharp attrition across treatment lines: only about one in four patients (25%) reached a third line of therapy, and just 6% reached a fourth—evidence that a large fraction of patients never benefit from later-line options and that mechanistically differentiated therapies are needed in the disease course. Lantern plans to position LP-184 initially in the third-line setting of advanced, metastatic bladder cancer where there is a high need for novel, mechanistically differentiated, biomarker driven therapy options. With roughly 25% of patients reaching third-line therapy, this represents an estimated addressable population of approximately 137,500 patients globally each year, with the majority of the commercial opportunity concentrated in the United States, Europe, and Japan. This persistent unmet need is further reflected by independent market analysts that value the current metastatic urothelial carcinoma therapy market at roughly USD 2,000 million, with projections approaching USD 4,000 million by 2030. LP-184 is an acylfulvene-class prodrug that is selectively activated by the enzyme PTGR1 (prostaglandin reductase 1), which is frequently overexpressed in urothelial and other cancers and has been associated with poorer prognosis. Once activated, LP-184 generates DNA damage that tumors depend on nucleotide-excision repair (NER) to fix. In tumors deficient in NER—particularly those with ERCC mutations—this creates a synthetic-lethal vulnerability, which co-occurring homologous-recombination defects may further sensitize. Approximately 10–15% of metastatic urothelial cancers harbor NER alterations, and PTGR1 overexpression is common in this tumor type. This dual mechanistic strategy—PTGR1 for activation and DDR deficiency for selective killing—is supported by Lantern’s preclinical patient-derived xenograft and isogenic model data and is more specific than most genomic- or protein-only selection strategies being pursued after first-line therapy. While many contemporary trials in this space focus on antibody-drug conjugates, FGFR inhibitors, or homologous-recombination-directed agents, the NER-focused acylfulvene approach remains largely unexploited. The open-label study employs a pragmatic two-part design.