Ruolin Liu

CONSORT diagram of enrolled, randomized, and treated patients in the study. MD, medical doctor; PD, progressive disease; SOC, standard of care. *Registration number was 78, one patient was registered twice.

Clinical outcomes of berzosertib + carboplatin and docetaxel + carboplatin. A and B, Waterfall plots of (A) maximal PSA decline and (B) decline in measurable lesions by RECIST 1.1 from baseline. One patient in arm B (Y, far right) had an unconfirmed PR at cycle 8, followed by progressive disease. C–E, Kaplan–Meier estimates of (C) rPFS, (D) PFS by PCWG3 criteria (“no longer clinically benefiting,” i.e., radiographic or clinical/symptomatic progression), and (E) OS.

HRD status does not demonstrate a statistically significant correlation with clinical benefit in either arm. Kaplan–Meier plots for PFS per PCWG3 criteria with patients across both arms and stratified by (A) HRD status determined by deleterious DDR gene mutations identified by WES of tumor biopsy, (B) RAD51 foci–based IHC, (C) DirectHRD analysis of WGS of cfDNA using a cutoff of 2.5 in the overall cohort, and (D) DirectHRD analysis of WGS of cfDNA using a cutoff of 2.5 in arm B only. NE, not estimable.

A combined ATM-RS biomarker identifies the best responders. A and B, Representative images of ATM (A) and pKAP1 (B) staining by IHC in tumor biopsy samples. The scale bar corresponds to 100 μm. C, Box plot showing pKAP1 levels in samples stratified by ATM status. Horizontal red lines depict the cutoff used to classify samples as ATM-RS–positive or ATM-RS–negative. D and E, Kaplan–Meier plots for PFS in patients across both arms (D) and in Arm B only (E), stratified by the combined ATM-RS classification.

Co-mut plot depicting variants in commonly altered genes in mCRPC (TP53, AR, PIK3CA, PTEN, RB1) and in HRR genes detected in tumor by whole exome sequencing (center triangles, blue) and in cfDNA by targeted panel sequencing at time point 1 (left triangles, purple) and time point 2 (right triangles, green).

Kaplan-Meier curves for PFS with patients stratified by HRD status determined by DirectHRD analysis of WGS data from cfDNA.

Kaplan-Meier curves for PFS stratified by ATM status by immunohistochemistry in tumor biopsy specimens, and scatter plot showing the relationship between PFS and % pKAP1 positivity in tumor biopsy specimens

Representativeness of Study Participants

TrAE among 65 patients who received assigned protocol treatment (worst grade by patient and toxicity type)