Abstract 600P
Background
Safety and initial efficacy results of a phase I dose-escalation study of a fractionated (dose-dense) regimen were previously described, without short-term dose-limiting toxicity [ESMO 2019]. Here, we report results of the complete phase I/II study.
Methods
Men with progressive mCRPC following at least 1 AR-pathway inhibitor (ARPI) and taxane chemo (or ineligible/refuse), intact organ function, and ECOG PS 0-2. Treatment: a single fractionated cycle of 177Lu-PSMA-617 on days 1 and 15 (7.4 to 22 GBq in dose-escalation cohort, followed by Simon 2-stage phase II study at 22GBq). PSMA expression was not a prerequisite for treatment, but baseline and post-treatment 68Ga-PSMA11 PET/CT and/or 177Lu-PSMA-617 SPECT performed. Follow up with serial PSA measurements, CT/bone scans, and circulating tumor cell (CTC; CellSearch) counts.
Results
50 men with median PSA 173.8, 35 (70%) CALGB (Halabi) poor risk. 47 (94%) with bone, 38 (76%) LN, 12 (24%) lung, 11 (22%) liver mets. 29 (58%) with ≥2 prior ARPI, 29 (58%) chemo, 14 (28%) radium-223, 2 (4%) 177Lu-J591. 27 (54%) treated at 22 GBq. 40 (80%) with any PSA decline, 27 (54%) with >50% PSA decline. Median PFS 5.6 mo [95%CI 3.9-8.0], radiographic PFS 9.6 mo [5.6-14.9], and OS 15.2 mo [10.8-27.0]. Of 31 with paired CTC counts, 16 (52%) decreased, 5 (16%) stable; 10 (32.3%) converted to favorable/undetectable. Adverse events included 38 (76%) pain flare, 27 (54%) xerostomia, 24 (48%) nausea, 21 (42%) fatigue, 17 (34%) thrombocytopenia, 10 (20%) anemia, 9 (18%) transaminitis, 5 (10%) neutropenia; All AEs restricted to Gr 1-2 except 4 (8%) with Gr 3 anemia. On multivariable analysis, higher PSMA uptake (p<0.005) and dose (p=0.06) associated with >50% PSA response and CALGB risk (p=0.032), prior chemo (0=0.041), higher PSMA uptake (0.085), and dose (p=0.072) associated with OS.
Conclusions
A single-cycle of fractionated-dose 177Lu-PSMA-617 is safe. Despite no pre-selection for PSMA expression, most have post-treatment PSA decline with favorable biochemical and radiographic progression-free survival compared to historical non-PSMA controls and similar to PSMA-selected studies administering multiple cycles in a less dose-intense fashion.
Clinical trial identification
NCT03042468.
Editorial acknowledgement
Legal entity responsible for the study
Weill Cornell Medicine.
Funding
Weill Cornell Medicine, Prostate Cancer Foundation, US Department of Defense, Endocyte.
Disclosure
S.T. Tagawa: Financial Interests, Personal, Research Grant: Endocyte; Financial Interests, Personal, Advisory Board: Endocyte; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Advisory Board: Novartis. O. Sartor: Financial Interests, Personal, Research Grant: Endocyte. N. Bander: Financial Interests, Personal, Leadership Role: BZL Biologics. All other authors have declared no conflicts of interest.