13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Animal studies to assess the carcinogenicity or mutagenic potential of flotufolastat have not been conducted. However, flotufolastat F 18 has the potential to be mutagenic because of the F 18 radionuclide. No studies in animals have been performed to evaluate potential impairment of fertility in males or females. Imaging Prior to Initial Definitive Therapy of Prostate Cancer The safety and efficacy of POSLUMA were evaluated in LIGHTHOUSE (NCT04186819), a prospective, multicenter, open-label, single-arm study in patients with prostate cancer who were candidates for initial definitive therapy. The study enrolled 356 patients diagnosed with unfavorable intermediate-risk (32%) or high-/very high- risk prostate cancer ( 68% ) who were candidates for radical prostatectomy and pelvic lymph node dissection (PLND). Unfavorable intermediate-risk was defined as having any ≥ 2 intermediate risk factors [T2b-T2c, Gleason score 7, PSA 10-20], Gleason pattern 4+3=7, or ≥ 50% of bio psy cores positive for prostate cancer. High or very high-risk was defined as having T3 or T4 disease, Gleason score ≥8, primary Gleason pattern 5, and/or PSA >20. 14 CLINICAL STUDIES 14.1 All patients received a single dose of POSLUMA with an administered radioactivity (mean ± SD) of 307 ± 23 MBq (8.3 ± 0.62 mCi), followed by PET/CT scan from mid-thigh to base of the skull. Three central readers blinded to clinical information independently interpreted each scan for lesions considered positive for prostate cancer in pelvic lymph nodes, categorized by subregion and left and right laterality [see Dosage and Administration (2.5 ) ] . Positive lesions in the prostate gland, lymph nodes outside the pelvis, soft tissue/parenchyma, and bones were also recorded. A total of 296 patients ( 83%) u nderwent standard-of-care prostatectomy and template PLND and had sufficient histopathology data for evaluation of the pelvic lymph nodes. The mean age was 65 years (range 46 to 82 years); distribution by race was 82 % White, 8% Black or African American, 0.3 % o ther, and 10 % unreported; and distribution by ethnicity was 5 % Hispanic/Latino, 86% non -Hispanic/Latino, and 9 % unreported. The median serum PSA was 8.4 ng/mL. The total Gleason score was 7 for 45 %, 8 for 26%, and 9 for 25% of the patients, with the remainder of the patients having Gleason scores of 6 or 10. Approximately 24 % of patients had pelvic lymph node metastases based on histopathology. POSLUMA performance was evaluated against histopathology after matching by hemipelvis. Table 6 shows the results, such that at least one true positive hemipelvis region defined a true positive patient. Table 6: Patient-Level, Hemipelvis Region-Matched Performance of POSLUMA PET for Detection of Pelvic Lymph Node Metastasis (N1) in LIGHTHOUSE N=296 Reader 1 Reader 2 Reader 3 True Positive 21 19 16
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Reference ID: 5180081
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