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)
Authors: Mittra Erik , Iagaru Andrei , Van der Veldt Astrid , Aloj Luigi , Wong Jeffrey , Djaileb Loic , Pathak Dhrubajyoti , Liu Yongmin , Solnes Lilja 
Published: April 2024

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 - &lt;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(7_Suppl):Abstract nr CT290.