COMBAT: A study of ⁶⁴Cu-SAR-BBN and ⁶⁷Cu-SAR-BBN for identification and treatment of GRPr-expressing metastatic castrate-resistant prostate cancer.

TPS247 Background: Metastatic castrate resistant prostate cancer (mCRPC) is an advanced and lethal form of prostate cancer. Prostate-specific membrane antigen (PSMA)-targeted theranostic agents, 68 Ga-PSMA-11 and 177 Lu-PSMA-617, have been approved by the FDA for patient selection and therapy for patients with mCRPC, respectively. Approximately 25% of patients with mCRPC show low or no PSMA expression. Consequently, these patients are unlikely to benefit from PSMA-targeted agents and represent a significant unmet need for both imaging and therapy. The Gastrin Releasing Peptide receptor (GRPr) is a transmembrane G-protein coupled receptor that is upregulated in many human cancers, including PC. A promising new theranostic pair, consisting of 64 Cu-SAR-BBN (imaging) and 67 Cu-SAR-BBN (therapy), targets the GRPr. This may offer a potential imaging and treatment option for patients with low or no PSMA expression. Methods: COMBAT is a multi-center, open-label, phase I/IIa dose-escalation and cohort expansion study of 64 Cu-SAR-BBN and 67 Cu-SAR-BBN administered to patients with mCRPC. Eligible patients will have progressive mCRPC, prior exposure to at least one androgen receptor pathway inhibitor, will be ineligible for 177 Lu-PSMA-617 therapy, and show a positive 64 Cu-SAR-BBN PET. This study is being conducted in 2 phases: a Dose Escalation Phase (n=up to 24) and a Cohort Expansion Phase (n=14). The primary and key secondary objectives include assessment of safety of 64 Cu- and 67 Cu-SAR-BBN, determining the maximum tolerated dose (MTD) or maximum feasible dose (MFD) and anti-tumor efficacy of 67 Cu-SAR-BBN. The 67 Cu-SAR-BBN dose levels investigated in the escalation phase include: 6 GBq (cohort 1, single dose with dosimetry assessment), 10 GBq (cohort 2, single dose), 14 GBq (cohort 3, single dose), and up to 28 GBq across two doses (cohort 4, two doses at MTD/MFD). Additional doses may be administered during the Dose Escalation Phase (maximum of 4 doses in each cohort). The Dose Expansion Phase of the study will allow the administration of up to 4 doses of 67 Cu-SAR-BBN at the MTD/MFD. Response measurements include reduction in PSA levels, radiological progression-free survival, duration of response, and overall survival. Radiological response will be assessed by RECIST 1 V1.1 and PCWG3. At the time of submission of this abstract, cohort 1 is open for enrollment. Clinical trial information: NCT05633160 .