3284 - Phase 1 Trial of 177 Lu -rhPSMA-10.1 Following PSMA-PET-Guided Post-Prostatectomy Salvage Radiotherapy: Early Response Assessment

Purpose/Objective(s): PET-guided post-prostatectomy salvage radiation therapy (RT), particularly with dose-escalation to PET-uptake sites, has demonstrated improved outcomes over conventional methods. To further improve outcomes, a Phase 1 (n=6) study was conducted for patients with post-prostatectomy recurrence and uptake on ¹⁸F-rhPSMA-7.3 PET in the prostate bed and/or pelvic nodes [without distant disease] undergoing salvage RT {with boost to PET uptake sites permitted} [+/- hormones] followed by adjuvant radioligand therapy (RLT) with 1-2 cycles of the novel radiohybrid radiopharmaceutical ¹⁷⁷Lu-rhPSMA-10.1. Dosimetry and early safety have been reported separately (SNMMI meeting, submitted) showing no SAE’s. Here we report initial RT response measured with post-RLT SPECT, early biochemical control, and acute toxicity.

Materials/Methods: Six patients received RT [± hormones] followed 3 weeks later with ¹⁷⁷Lu-rhPSMA RLT. Cohort 1 (n=3) was assigned a single cycle with a target administered activity of 5.0 GBq (135.0 mCi) ± 20%, while Cohort 2 (n=3) was assigned two cycles of the same dose, separated by six weeks. Two SPECT/CT acquisitions per cycle (days 1–3 and 4–7) were done for post-treatment dosimetry. The first (days 1-3) post-treatment SPECT/CT from the first cycle was used in this sub-analysis for all 6 patients to assess response to RT and compared with corresponding pre-treatment ¹⁸F-rhPSMA-7.3 PET lesion using the t-test. PSA and provider-reported genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v5.0) were collected.

Results: Characteristics: median age: 69.0 years; race: 5 white, 1 AA; Gleason: 6:n=1, 7:n=3, 9:n=2; node: pN0: n=4, pN1: n=2; pre-XRT PSA: median: 0.24; range (0.03-2.98 ng/mL). There were 12 total uptake sites on the pre-treatment ¹⁸F-rhPSMA-7.3 PET (prostate bed (PB): n=7; pelvic LNs: n=5). RT Fields: PB only: n=4; PB+LN’s: n=2; Beam: photons: n=5; protons: n=1; ADT use: yes: n=4; no: n=2. PB received 66.6/1.8 Gy with SIB to 74.0/2.0 Gy for all 7 lesions. Pelvic LN’s received 45.0/1.8Gy with 1 pt having SIB to 50.0/2.0Gy. Post-RT and post-RLT (first cycle) the uptake on the initial SPECT/CT (day 1-3) acquisition was completely absent in all 12 previously identified ¹⁸F-rhPSMA-7.3 PET-positive lesions (p <0.001). Maximum acute toxicity: (GU: grade 2 (n=4), grade 1 (n=2); GI: grade 1 (n=4), grade 0 (n=2)); {no = grade 3 GU/GI events}. At most recent follow-up (range 2.0 – 21.0 months), PSA values (ng/mL) were: 0.28 (n=1), 0.06 (n=1), <0.01 (n=4); most recent toxicity: (GU: grade 1 (n=3), grade 0 (n=3); GI: grade 1 (n=1), grade 0 (n=5)).

Conclusion: Within limitations in using dosimetry SPECT to evaluate response, pre-treatment PSMA PET uptake appeared completely resolved on initial SPECT (assessing ADT+RT response) in all 12 lesions over 6 patients in this phase 1 study, with excellent PSA control and tolerability. These data suggest a promising role for post-RT RLT in this setting; a randomized trial is planned at our institution to rigorously test this hypothesis.