Study launches of novel theranostic for 177Lu-PSMA-617–ineligible mCRPC

The phase 1/2 COMBAT study has launched examining the novel theranostic ^64Cu/67Cu-SAR-Bombesin (BBN) in patients with gastrin releasing peptide receptor (GRPr)-expressing metastatic castration-resistant prostate cancer (mCRPC) who are ineligible for ¹⁷⁷Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan; Pluvicto).¹

“Around a quarter of men with mCRPC do not have PSMA-expressing lesions, making it impossible to offer PSMA-targeted products as therapy for this group of patients. As a very large proportion of prostate cancers express GRPr, SAR-Bombesin is an exciting new prospect for better treating these patients that have few therapeutic options at present,” said Dr Alan Taylor.

Clarity Pharmaceuticals, the company developing the treatment, reported in a press release that the first clinical site for the trial (NCT05633160) opened at BAMF Health, Inc, in Michigan.¹

The pan-cancer radiopharmaceutical SAR-Bombesin targets GRPr, which is found on tumor cells in several cancers. According to CLARITY, GRPr is present in most prostate tumors, including those that test negative for PSMA.¹

The theranostic ^64Cu/67Cu-SAR-BBN combines the imaging product ⁶⁴Cu-SAR-BBN and the targeted therapy ⁶⁷Cu-SAR-BBN. In the open-label, single-arm, dose-escalation/expansion COMBAT trial, ⁶⁴Cu-SAR-BBN will be used for the selection of appropriate patients to receive treatment with ⁶⁷Cu-SAR-BBN.¹ 

The study aims to enroll up to 38 patients at clinical locations in the United States. To enroll on the trial, patients must have mCRPC, an ECOG performance status of 0 to 2, and a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L). Individuals with symptomatic brain metastases are not eligible to enroll.²

The estimated study completion date for the COMBAT trial is May 2026.²

¹⁷⁷Lu-PSMA-617 is approved for the treatment of patients with PSMA-positive mCRPC who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The agent was approved in 2022 based on findings from the VISION trial.³

"We are excited to initiate our first theranostic clinical trial of the SAR-Bombesin product. COMBAT is our third theranostic trial in the United States and a second theranostic trial in prostate cancer, an indication that continues to have a high unmet need. In the VISION trial for the recently approved ¹⁷⁷Lu PSMA-617, median overall survival increased from approximately 11 months on standard of care therapy to approximately 15 months with ¹⁷⁷Lu PSMA-617 plus standard of care. Despite this, around a quarter of men with mCRPC do not have PSMA-expressing lesions, making it impossible to offer PSMA-targeted products as therapy for this group of patients. As a very large proportion of prostate cancers express GRPr, SAR-Bombesin is an exciting new prospect for better treating these patients that have few therapeutic options at present in the face of a devastating diagnosis,” Dr Alan Taylor, executive chairman, Clarity, stated in the press release.¹

"We look forward to progressing the COMBAT trial and building on the compelling data from our preclinical studies as well as from three diagnostic trials with this product. SAR-Bombesin has already resulted in improvements to the management of prostate cancer for patients with PSMA-negative or low PSMA expressing tumors and we hope to confirm its safety and efficacy in the theranostic trial," added Taylor.¹

References

1. Clarity Pharmaceuticals. Clarity commences COMBAT theranostic prostate cancer trial in the US. Published online June 19, 2023. Accessed June 19, 2023. https://www.prnewswire.com/news-releases/clarity-commences-combat-theranostic-prostate-cancer-trial-in-the-us-301855052.html

2. NIH US National Library of Medicine ClinicalTrials.gov. 64Cu-SAR-BBN and 67CU SAR-BBN for Identification and Treatment of Gastrin Releasing Peptide Receptor (GRPR)-Expressing Metastatic Castrate Resistant Prostate Cancer in Patients Who Are Ineligible for Therapy With 177Lu-PSMA-617 (COMBAT). Last updated June 18, 2023. Accessed June 19, 2023. https://clinicaltrials.gov/ct2/show/NCT05633160

3. US Food & Drug Administration. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. Published online March 23, 2022. Accessed June 19, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer