Rezvilutamide (REZ) plus docetaxel (DOC) in patients (pts) with chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) after progression on abiraterone (ABI).

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5059 Background: Despite DOC is recommended for chemo-naïve mCRPC pts previously treated with novel hormone therapy, prognosis remains unfavorable. Herein we report the safety, PK, and preliminary efficacy of addition of REZ (a novel androgen receptor inhibitor) to DOC in chemo-naïve mCRPC pts who had progressed after ABI. Methods: This was a multicenter, 2-part, phase 2 study. Part 1 included a 3 + 3 dose escalation phase and a dose expansion phase. Eligible pts were enrolled to receive REZ (160/240 mg, PO, QD) plus DOC (75 mg/m2, IV, D1, Q3W, up to 10 cycles [C]), followed by REZ monotherapy (240 mg, PO, QD). REZ was given continuously staring from C1D2. DOC was concurrent with prednisone (5 mg, PO, BID). Both dose levels of REZ were selected to be expanded. Primary endpoint of part 1 was safety. Results: As of Aug 31, 2023, 36 pts were enrolled (18 with REZ 160 mg plus DOC and 18 with REZ 240 mg plus DOC). In the REZ 160 mg plus DOC and REZ 240 mg plus DOC groups, rate of pts with ECOG PS of 1 was 83.3% and 61.1%, rate of pts with Gleason score ≥ 8 was 88.9% and 72.2%, rate of pts with >10 bone metastases was 66.7% and 44.4%, and median baseline prostate-specific antigen (PSA) level was 81.7 ng/mL (range: 2.7-5993.0) and 144.0 ng/mL (2.9-3720.0). No DLTs were reported. Treatment-related adverse events of grade ≥ 3 occurred in 32 (88.9%) pts (14 [77.8%] pts with REZ 160 mg plus DOC, and 18 [100.0%] pts with REZ 240 mg plus DOC), with the most common being decreased neutrophil count, decreased white blood cell count, and anemia. C2/C1 ratio of AUC0-24h and Cmax of DOC was 0.73 and 0.78 when combined with REZ 160 mg, while that was 0.58 and 0.68 when combined with REZ 240 mg, which indicated influence of CYP3A strong inducer REZ on CYP3A4 substrate DOC with stronger impact at REZ 240 mg. Rate of PSA response at week 12 was 75.0%, time to PSA progression was 10.5 mo (95% CI, 5.6-11.3), and radiological PFS was 13.8 mo (95% CI, 5.7-19.6) with REZ 160 mg plus DOC, while that with REZ 240 mg plus DOC was 60.0%, 14.1 mo (95% CI, 4.1-21.4), and 8.5 mo (95% CI, 5.6-not reached) (Table). Conclusions: REZ plus DOC was well tolerated with promising efficacy in chemo-naïve mCRPC pts who had progressed after ABI. Clinical trial information: NCT04603833 . [Table: see text]

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