Abstract CT290: Trial in progress: Evaluation of the safety, tolerability, whole-body distribution, radiation dosimetry and antitumor activity of 177Lu-NeoB in patients with advanced solid tumors expressing gastrin-releasing peptide receptor (GRPR)

Abstract Introduction: Many common cancers such as breast, lung, and prostate, plus several less common malignancies such as gastrointestinal stromal tumors (GIST) and glioblastoma (GBM) express or are associated with the Gastrin-Releasing Peptide Receptor (GRPR). Therefore, GRPR could be utilized for the development of innovative approaches to tumor imaging and therapeutic interventions. NeoB is a new generation bombesin analog, which binds to GRPR with high affinity/specificity. The structure of NeoB permits radiolabeling with gallium-68 68Ga (for imaging) or lutetium-177 177Lu (for therapy), making it suitable for theranostics. Pre-clinical and early phase clinical data confirmed the utility of 68Ga-NeoB for identification of GRPR-expressing tumors and demonstrated the in vitro and in vivo antitumor activity of 177Lu-NeoB. In the Phase IIa part of this first-in-human study of 177Lu-NeoB (NeoRay; NCT03872778), we aim to characterize the safety, tolerability, whole-body distribution, radiation dosimetry and antitumor activity of 177Lu-NeoB in patients with selected advanced solid tumors known to express GRPR. Methods: The Phase IIa part of this Phase I/IIa multi-center, open-label study will enroll approximately 50 adult patients (age ≥18 years old) with advanced/metastatic cancers and for whom no standard therapy is available, tolerated or appropriate. Patients will be enrolled across 4 cohorts: HR-positive, HER2-negative breast cancer (Cohort A), prostate cancer (Cohort B), GIST (Cohort C) or any solid tumor overexpressing GRPR including recurrent GBM, and who have moderate renal impairment (CrCl ≥30 mL/min - 60 mL/min; Cohort D). Eligible patients must have at least one measurable lesion with confirmed uptake of 68Ga-NeoB and have an ECOG performance status of ≤1. Patients will be treated with 177Lu-NeoB at the recommended Phase II dose (9. 25 GBq 250 mCi) for a minimum of 2 treatment cycles, each lasting 6 weeks. The primary endpoints are assessment of the disease control rate with 177Lu-NeoB in cohorts A, B and C, and evaluation of the pharmacokinetics (PK), biodistribution and radiation dosimetry in patients with impaired renal function (Cohort D). Secondary endpoints include assessment of the antitumor activity, PK, distribution, radiation dosimetry, and impact on the quality of life of patients in the 177Lu-NeoB cohorts (A, B and C) as well as the safety and tolerability of both 177Lu-NeoB and 68Ga-NeoB across all cohorts. Citation Format: Erik Mittra, Andrei Iagaru, Astrid Van der Veldt, Luigi Aloj, Jeffrey Wong, Loic Djaileb, Dhrubajyoti Pathak, Yongmin Liu, Lilja Solnes. Trial in progress: Evaluation of the safety, tolerability, whole-body distribution, radiation dosimetry and antitumor activity of 177Lu-NeoB in patients with advanced solid tumors expressing gastrin-releasing peptide receptor (GRPR) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT290.