Dose fractionation (DF) and combination radioimmunotherapy (RIT) in patients with prostate cancer using 177Lu-J591 (Lu-J591) anti-PSMA antibody and docetaxel

360 Objectives We have previously performed phase I and II clinical studies with Lu-J591 mAb radioimmunotherapy (RIT) in patients with metastatic castration-resistant prostate cancer (metCRPC). MTD was 70 mCi/m2. In order to reduce myelotoxicity, increase the amount of total administered dose, and improve efficacy, we have designed two phase I trials to evaluate DF alone and in combination with docetaxel, which is standard chemotherapy for metCRPC, and is a known radiosensitizer. Methods In the first phase I study, cohorts of 3-6 patients with progressive metCRPC received 2 FD of Lu -J591, 2 weeks apart: In a second phase I trial, patients with metCRPC received docetaxel (75 mg/m2 every 3 wks) with prednisone 10 mg/d. In both trials, Group-1 was started with two doses of Lu-J591 at 20 mCi/m2, 2 wks apart, and then escalated in 5 mCi/m2 increments to 45 mCi/m2. Results In the DF trial, 28 patients have been treated, receiving up to 45 mCi/m2 x2 (highest anticipated dose). Despite achieving cumulative doses exceeding the single-dose MTD (a dose at which 41% require platelet transfusions), only 6 pts receiving up to 90 mCi/m2 experienced Gr 4 thrombocytopenia (2 requiring a transfusion). 3 pts experienced Gr 4 neutropenia without fever; no growth factors were needed. Gr >1 non-heme toxicity has been rare. The MTD for the regimen is 40 mCi/m2 x2 (no transfusions needed at this dose). 13 (46%) pts have experienced PSA declines. In the second combination RIT trial, the first group (n=3) received docetaxel and Lu-J591 (20 mCi/m2x 2). In the next cohort , one subject received docetaxel and Lu-J591 (skipped to dose level 3 = 30 mCi/m2 x2). No DLT has been observed so far. Conclusions With DF, paatients are able to tolerate higher cumulative doses than with single-dose Lu-J591 and some efficacy has been demonstrated. MTD with combination RIT has not been determined in metCRPC