Safety and antitumor activity of ¹⁷⁷ Lu-catelase: A preliminary clinical study in soft tissue sarcoma.

Abstract

11563 Background: Localized radiotherapy with radioisotope injections holds promise but is limited by poor tumor retention and hypoxia. To overcome these challenges, we developed 177 Lu-CAT/ALG, a hydrogel formulation containing catalase labeled with 177 Lu and sodium alginate (ALG). Upon injection, endogenous calcium rapidly forms a hydrogel, securing 177 Lu-CAT within the tumor, alleviating hypoxia, and enhancing therapeutic efficacy. Preclinical studies demonstrated sustained hypoxia relief, superior tumor retention, and significant antitumor activity. This phase 1 trial evaluates the safety and preliminary efficacy of 177 Lu-CAT/ALG in patients with soft tissue sarcoma (STS). Methods: Patients with locally advanced STS underwent baseline metabolic and volumetric assessments using 18 F-FDG PET/MR imaging. Intratumoral doses were calculated using the OLINDA 2.0 Sphere Model, with ultrasound-guided injections administered every 8 weeks. SPECT imaging assessed tumor retention at 2, 24, 96, and 168 hours post-injection. Efficacy was evaluated bi-monthly per PERCIST criteria. Primary endpoints included tumor retention and safety (CTCAE v5.0). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Seven patients with locally advanced STS were treated, with a median tumor size of 8.5 cm. SPECT imaging confirmed that at least 60% of 177 Lu-CAT/ALG remained within tumors at 168 hours. The most common adverse events (AEs) were grade 1-2 reductions in white blood cell count (4/7 patients). One patient experienced a grade 4 AE (thrombocytopenia). Stable disease was observed in two patients, with disease control lasting 16.53 and 12.8 months. As of the data cutoff, one patient remains on treatment. Pathological analysis of a tumor specimen from a patient with increased tumor volume on PET/MR revealed 70% necrosis after resection. Conclusions: 177 Lu-CAT/ALG demonstrated a favorable safety profile, sustained tumor retention, and encouraging antitumor activity in patients with locally advanced STS. These results highlight the potential of 177 Lu-CAT/ALG as a novel therapeutic approach and support further evaluation in larger trials. Clinical trial information: NCT05985278 . Characteristics of participants. No. Gender Age Tumor type Primary tumor location Tumor size Number of injections Mean dose of injections (range)/mCi Outcomes 1 F 41 LGSTS, NOS right scapular region 8.6 5 23.30(16.8-29.1) On treatment 2 F 55 FS Right chest wall 9.3 1 14.3 PD 3 F 58 LGSTS, NOS Left chest wall 4.7 4 9.6 (7.0-10.7) PD 4 F 51 LMS Abdominal wall 7.3 1 31.9 PD 5 F 47 EMFS Right chest wall 9.6 1 32.4 PD 6 M 60 UPS Neck 7.6 1 23.8 PD 7 M 67 MFS Right elbow 8.5 1 15.7 PD LGSTS: low grade soft tissue sarcoma, NOS: not otherwise specified, FS: fibrosarcoma, LMS: leiomyosarcoma, EMFS: epithelioid myxofibrosarcoma, UPS: undifferentiated pleomorphic sarcoma, MFS: myxofibrosarcoma, PD: progressive disease.