NorthStar Medical Radioisotopes has received FDA acceptance of its Type II Drug Master File for no-carrier-added Actinium-225, a radioisotope used in cancer treatment. The approval allows pharmaceutical partners to reference NorthStar's manufacturing and quality controls in their drug applications, streamlining regulatory pathways for targeted alpha therapy development. The Beloit, Wisconsin-based company produces Ac-225 using an electron-accelerator irradiation process combined with purified Radium-225 sources. NorthStar announced commercial-scale production of the isotope in January 2026. The DMF acceptance establishes NorthStar as a regulatory-ready supplier for targeted alpha therapies, supporting partners from clinical development through commercialisation. The company also produces copper-67 and operates a radiopharmaceutical contract development and manufacturing organisation.

NorthStar: LCT plus osimertinib boosts PFS in metastatic EGFR+ NSCLC. Combining local consolidative therapy with osimertinib enhances progression-free survival in metastatic EGFR-mutant non-small cell lung cancer patients. The addition of local consolidative therapy (LCT) to osimertinib (Tagrisso) significantly improved progression-free survival (PFS) vs osimertinib alone in patients with metastatic EGFR-mutant non - small cell lung cancer (NSCLC), even in the setting of polymetastatic disease, according to data from the phase 2 NorthStar trial (NCT03410043) presented during the 2025 ESMO Congress.[1] The median PFS with osimertinib plus LCT (n = 56) was 25.3 months (95% CI, 19.4-45.0) vs 17.5 months (95% CI, 14.5-24.3) with osimertinib alone (n = 63), translating to a 34% reduction in the risk of disease progression or death (HR, 0.66; 95% CI, 0.50-0.87; 1-sided log rank P = .025). When broken down by EGFR mutation subtype, among those with exon 19 deletions who received osimertinib plus LCT (n = 34), the median PFS was 39.8 months (95% CI, 25.4-58.7) vs 22.4 months (95% CI, 17.0-35.7) with osimertinib alone (n = 44; HR, 0.57; 95% CI, 0.40-0.82). In those with exon 21 L858R mutations, the median PFS with osimertinib plus LCT (n = 19) was 19.0 months (95% CI, 15.4-36.6) vs 11.0 months (95% CI, 6.4-20.9) with osimertinib alone (n = 22; HR, 0.60; 95% CI, 0.39-0.92). Within those who had no more than 3 metastases at randomization, those given osimertinib plus LCT (n = 24) experienced a median PFS of 33.1 months (95% CI, 23.9-not applicable [NA]) vs 22.4 months (95% CI, 12.5-NA) with osimertinib monotherapy (n = 26; HR, 0.67; 95% CI, 0.43-1.03). In those with more than 3 metastases, osimertinib plus LCT (n = 32) led to a median PFS of 19.7 months (95% CI, 15.4-48.3) vs 15.9 months (95% CI, 13.8-23.9) with single-agent osimertinib (n = 37; HR, 0.70; 95% CI, 0.50-1.00). Complete LCT was achieved in 59% of patients with polymetastatic disease at baseline; these patients experienced a median PFS of 27.9 months (95% CI, 16.6-48.3); those who received partial LCT had a median PFS of 14.5 months (95% CI, 10.2-21.6). "These findings support osimertinib plus LCT as a safe and effective strategy to extend disease control and delay systemic progression in advanced EGFR-mutant NSCLC," Yasir Y. Elamin, MD, said in a presentation of the data during the meeting. Elamin is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, in Houston. What unmet need did the NorthStar study seek to address? The majority of patients with metastatic EGFR-mutated NSCLC who receive treatment with EGFR TKIs experience resistance and progressive disease. For patients with oligometastatic disease, LCT with radiotherapy or surgery has boosted outcomes. Although it has been hypothesized that pairing LCT with EGFR TKIs such as osimertinib could lead to the elimination of resistant clones and defer systemic progression, there is no prospective, randomized evidence pertaining to the role of this approach, Elamin noted. What was the design of the NorthStar trial in egfr-mutated NSCLC? The multicenter, randomized, phase 2 trial[1,2] enrolled patients with locally advanced or metastatic NSCLC who had measurable disease, an ECOG performance status no higher than 1, and TKI-naive EGFR exon 19 deletions or L858R mutations, or acquired T790 mutations without prior exposure to a third-generation TKI. After receiving induction osimertinib for 6 to 12 weeks, those without progressive disease (n = 120) were randomly assigned 1:1 to receive osimertinib or osimertinib plus LCT, with EGFR TKI given until progressive disease or intolerable toxicity. Patients were stratified based on if they were TKI naive or received a prior first- or second-generation TKI (yes vs no), number of metastases (<=3 vs >3), had a partial response (PR) or stable disease (SD) to induction osimertinib, and presence of brain metastases (yes vs no). LCT modalities (n = 56) included radiation (58.9%), surgery (32.1%), and both (9%). Among the 23 patients who underwent surgical procedures (n = 23), 78.3% received lobectomy, 8.7% had wedge resection, 4.3% had lobectomy and wedge resection, 4.3% had segmentectomy, and 4.3% had adrenalectomy. Radiation modality (n = 50) included volumetric modulated arc therapy or intensity modulated radiation therapy (56%), stereotactic body radiation therapy (30%), and 3D conformal or 2D conformal (14%). The primary end point of the study was PFS, and secondary end points comprised safety of the combination, overall survival, PFS in those with up to 3 metastases, and PFS in those who did not have exposure to TKIs. Elamin noted that with 120 patients undergoing randomization, the study had 80% power to detect an 8-month improvement in median PFS with a 1-sided type I error of 0.1. Leveraging O'Brien-Fleming outer test boundaries, the 1-sided Z-score boundary for rejecting the null hypothesis was - 1.316, which corresponds to a P value of .094. HR was evaluated using the Cox proportional hazard model, and PFS was calculated from the time that osimertinib was initiated to the date of disease progression or death using the Kaplan-Meier survival method. What should be known about the patient population of NorthStar? The median patient age was 64 years (range, 31-82) in the osimertinib-alone arm (n = 63) and 66 years (range, 40-88) in the osimertinib/LCT arm (n = 56). More than half of patients were women (66.7% vs 66.1%, respectively). In the osimertinib-alone arm, 66.7% of patients had EGFR exon 19 deletions, 28.5% had exon 21 L858R mutations, and 4.8% had T790M mutations (with L858R or exon 19 deletion); in the osimertinib/LCT arm, these respective rates were 57.1%, 39.3%, and 3.6%. Most patients were TKI naive (95.2% vs 96.4%), had more than 3 metastases at baseline (71.4% vs 69.6%), and greater than 3 metastases at randomization (58.7% vs 57.1%). More than half of patients in both arms did not have brain metastases (63.5% vs 62.5%). In the osimertinib monotherapy arm, 68.3% of patients experienced a PR to induction osimertinib, and 31.7% had SD; in the osimertinib/LCT arm, these respective rates were 71.4% and 28.6%. Eighty-four patients had polymetastatic disease at baseline. Of these patients, 29% had 0 to 5 metastatic lesions, 43% had 6 to 10 lesions, and 29% had more than 10 lesions. "Pleural effusion [27%] and lymphangitic spread [14%] were common, reinforcing that this is, indeed, a real-world population with a heavy disease burden," Elamin underscored. What was learned about the safety profile of osimertinib plus LCT? In the osimertinib/LCT arm (n = 56), the most common treatment-related adverse effects (AEs) included skin disorders (grade 1-2, 64.4%; grade 3, 1.8%), paronychia (57.6%; 0%), fatigue (55.3%; 0%), diarrhea (46.4%; 3.6%), dry skin (33.9%; 0%), dyspnea (30.3%; 0%), cough (28.6%; 0%), musculoskeletal pain (27.1%; 0%), nausea or vomiting (16.9%; 0%), thrombocytopenia (16.6%; 1.8%), anorexia (16.1%), constipation (14.3%; 1.8%), dysphagia (12.5%; 0%), transaminitis (11.9%; 0%), anemia (10.7%; 0%), leukopenia (10.7%; 1.8%), pleural effusion (10.7%; 1.8%), pneumonitis (10.7%; 1.8%), and hyponatremia (8.9%; 7.1%). LCT-specific AEs included pneumonitis (grade 1, 1.8%; grade 2, 8.9%; grade 3, 1.8%), dyspnea (26.8%; 3.6%; 0%), arterial injury (0%; 0%; 1.8%), empyema (0%; 0%; 1.8%), esophagitis (1.8%; 1.8%; 0%), and dysphagia (12.5%; 0%; 0%). No grade 4 or 5 LCT-related AEs occurred. "No excess toxicity was observed - in particular, there was no increased rate of pneumonitis beyond that expected with thoracic radiation," Elamin concluded. Disclosures: Elamin disclosed receipt or advisory fees from AstraZeneca, Eli Lilly, Novartis, Sanofi, Takeda, BMS, Nuvation, Mirati, Merus, Tahioo, BluePrint Medicines, Catalyst Pharmaceuticals, Johnson & Johnson, and Kestrel Therapeutics; and research support (institution) from AstraZeneca, Takeda, Nuvation, Nuvalent, Merus, Tahioo, Telligene, and Ellipses. 1. Elamin YY, gandhi SJ, antonoff MB, et al. NorthStar: A phase II randomized study of osimertinib (osi) with or without local consolidative therapy (LCT) for metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Presented at: 2025 ESMO Congress; october 17-21, 2025; berlin, germany. Abstract LBA72. 2. Osimertinib, surgery, and radiation therapy in treating patients with stage IIIB or IV non-small cell lung cancer with EGFR mutations, NORTHSTAR study. ClinicalTrials.gov. Updated june 11, 2025. Accessed october 17, 2025. Stay up to date on practice-changing data in community practice.

NorthStar will supply non-carrier added Actinium-225, a radionuclide, for use with Ariceum's first-in-class radiopharmaceutical drug, satoreotideBERLIN and BELOIT, Wis., Dec. 11, 2024 /PRNewswire/ -- Ariceum Therapeutics, a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, and NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, today announced the signing of a supply agreement for the therapeutic medical radioisotope, Actinium-225 (Ac-225). Under the terms of the agreement, NorthStar will provide Ariceum with non-carrier-added (n.c.a.), high purity, Ac-225, a rare and critical isotope that is in high demand, providing Ariceum with an additional clinical source of supply for its evolving pipeline development programs. Ariceum will use NorthStar's Ac-225 to radiolabel its proprietary peptide (SS0110) satoreotide, a first-in-class antagonist of the somatostatin receptor 2 (SSTR2). Satoreotide is being developed as a 'theranostic pair' for the combined diagnosis and targeted radionuclide treatment of multiple indications expressing SSTR2, such as small cell lung cancer (SCLC), pancreatic cancers, Merkel Cell Carcinoma, and other aggressive cancers. Manfred Rüdiger, Chief Executive Officer of Ariceum Therapeutics, commented: "Satoreotide is the first Ac-225 labelled antagonist of the SSTR2 receptor targeting SCLC