LUNAR : a randomized Phase 2 study of 177 Lutetium‐PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (clinical trial protocol)

Objective To assess the efficacy of 177 Lu‐PNT2002, a novel radiolabelled small molecule that binds with high affinity to prostate‐specific membrane antigen (PSMA), in combination with stereotactic body radiotherapy (SBRT) to all sites of metastasis, vs SBRT alone, in men with oligorecurrent metastatic hormone‐sensitive prostate cancer (mHSPC). Patients and Methods The 177 Lutetium‐PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR) trial is an open‐label, randomized, stratified, two‐arm, single‐centre, Phase 2 trial to compare the efficacy and safety of neoadjuvant 177 Lu‐PNT2002 plus SBRT vs SBRT alone in men with oligorecurrent mHSPC. Key eligibility criteria include one to five lesions identified on a PSMA positron emission tomography (PET)/computed tomography (CT) scan centrally reviewed by a board‐certified nuclear medicine physician. Key exclusion criteria include castrate‐resistant disease, de novo oligometastatic disease and receipt of androgen deprivation therapy (ADT) within 6 months of trial enrolment. The trial aims to enrol 100 patients who will be centrally randomized to one of the two treatment arms, in a 1:1 ratio. Patients in the control arm receive SBRT to all sites of disease. Patients in the experimental arm receive two cycles of neoadjuvant 177 Lu‐PNT2002 (6.8 GBq) 6–8 weeks apart, followed by an interval PSMA PET/CT in 4–6 weeks and dose‐adapted SBRT to all sites of disease 1–2 weeks later. The primary endpoint is progression‐free survival. Secondary endpoints are radiographic and prostate‐specific antigen‐based progression, acute and late physician‐scored toxicity, patient‐reported quality of life, ADT‐free survival, time to progression, overall survival, locoregional control, and duration of response. Enrolment in the study commenced in September 2022. Results and Conclusions The addition of 177 Lu‐PNT2002 to metastasis‐directed therapy alone may potentially further forestall disease progression. The results of this Phase 2 trial will determine, for the first time in a randomized fashion, the added benefit of 177 Lu‐PNT2002 to SBRT in patients with oligorecurrent mHSPC.