RT Journal Article SR Electronic T1 Interim results of a Phase I/II prospective dose escalation trial evaluating safety and efficacy of combination 177Lu PSMA 617 and NOX66 in men with mCRPC post androgen signalling inhibition and 2 lines of taxane chemotherapy (LuPIN trial). JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 465 OP 465 VO 60 IS supplement 1 A1 Emmett, Louise A1 Crumbaker, Megan A1 Nguyen, Andrew A1 Ho, Bao A1 Yin, Charlotte A1 Isheish, Noah A1 Azad, Arun A1 Violet, John A1 Sharma, Shikha A1 Joshua, Anthony YR 2019 UL http://jnm.snmjournals.org/content/60/supplement_1/465.abstract AB 465Background: Despite treatment advances, metastatic castrate resistant prostate cancer (mCRPC) remains a lethal disease. Trials in 177LuPSMA - 617 have demonstrated good efficacy and safety, but not all men respond to treatment, and treatment responses may be limited in duration. Idronoxil is an inhibitor of external NADH oxidase type 2 and has a variety of downstream pro-apoptotic actions including radio-sensitization. We present preliminary results of a phase 1/2 dose escalation trial of LuPSMA and NOX66 in men with heavily pre-treated mCRPC. Methods: 16 men with mCRPC progressing despite docetaxel, cabazitaxel and either abiraterone or enzalutamide were enrolled. Imaging criteria included a PSMA PET/CT intensity SUV max >10 at all sites of measurable disease with no discordant disease on FDG PET/CT. Men required Hb >10ng/mL, Platelets >90 and GFR >40 mls/min. All men received up to 6 doses of 177 Lu-PSMA 617 at 6-weekly intervals; the first 8 men received 400mg idronoxil (suppository) daily cycle days 1-10. Following safety data review, the dose for patients 9-16 was escalated to 800mg idronoxil daily. All men received Dexamethasone 8mg on Day 1 and 4mg days 2,3. Results: To date, all 16 men have received ≥2 doses and 4/16 (25%) 6 cycles. The treatment has been well tolerated. Adverse events (AEs) and PSA responses are summarized in the table below; 1/16 reported an SAE due to pneumonitis and continued on trial without NOX66. 3/16 (19%) have exited trial prematurely due to progressive disease.View this table: Conclusions: Combination LuPSMA-617 + NOX66 demonstrate encouraging early results. Based on these findings, particularly safety, recruitment for a phase II expansion cohort is underway.