Results
pneumonitis, death, pembrolizumab, tumours, toxicities, deaths
PNEUMONITIS, INFLAMMATORY ARTHRITIS, DISEASE PROGRESSION, ADVERSE EVENTS, TUMOURS, DISEASE, EVENT, MAY, ADVERSE EVENT, ASPIRATION PNEUMONIA
Between Aug 8, 2019, and May 7, 2022, 59 male patients were screened, of whom 43 were enrolled (18 patients in part A; 25 patients in part B) and received one dose of protocol therapy (In part A of the study, no dose-limiting toxicities were observed. Schedule 1 (In part B, 14 (56%; 95 CI% 35–76) of 25 patients had a confirmed objective response (In the overall study cohort, two (5%) of 43 patients had a grade 3 or worse treatment-related adverse event (grade 3 inflammatory arthritis in schedule 2 [n=1] and grade 3 pneumonitis in schedule 3 [n=1]). The most common treatment-related adverse events are shown in One serious adverse event (death due to aspiration pneumonia), no treatment-related serious adverse events, and no treatment-related deaths were observed. Overall, sixteen (37%) of 43 patients died; 15 were due to disease progression and one death was due to aspiration pneumonia. No delayed immune-related adverse events were observed that occurred more than 30 days after the final dose of pembrolizumab.In the overall cohort (n=43), best overall response included two patients (5%) with complete response, 20 (47%) patients with confirmed partial response, 12 (28%) of patients with stable disease, and nine (21%) patients with progressive disease (19 (44%; 95% CI 29–59) of 43 patients had a PSA50 response and seven (16%; 5–27) of 43 patients had a PSA90 response (39 (91%) of 43 patients had a radiographical progression event. The median progression-free survival was 6·9 months (95% CI 3·9–7·0), and 22 (51%; 35–67) of 43 patients were alive and progression free at 6 months (Subsequent anti-cancer therapies are summarised in the All patients who had an objective response had tumours that were microsatellite stable and had a low mutational burden on targeted somatic genomic sequencing (data not shown). Three patients harboured somatic pathogenic mutations in the homologous recombination deficiency pathway (Seven patients had one or more PSMA-negative soft tissue lesion on PET at enrolment. Three (43%) of seven patients had clinical benefit (two with stable disease for >6 months, one with confirmed objective response).91 evaluable metastatic soft tissue lesions were identified. Baseline maximum standardised uptake value (SUVFollow-up PSMA PET scans were obtained at the time of radiographical or clinical progression in 18 (42%) of 43 patients, with a total of 34 evaluable soft tissue lesions. At progression, follow-up PSMA PET imaging showed PSMA expression was lower than at baseline (mean SUVEight patients received at least one dose of An exploratory analysis of circulating immune cell subsets from patients enrolled in part A (n=18) showed that pembrolizumab reduced PD-1 staining in T-cell populations (