Pembrolizumab (pembro) plus docetaxel and prednisone in patients (pts) with abiraterone acetate (abi) or enzalutamide (enza)-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort B efficacy, safety and, biomarker results.

Abstract

5550 Background: Pembro + docetaxel and prednisone (cohort B) has shown antitumor activity in pts with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated efficacy and safety and new biomarker data from cohort B are reported. Methods: Pts who received at least 4 wk of abi or enza in the prechemotherapy mCRPC setting and whose disease progressed within 6 mo of screening were eligible. Pts received pembro 200 mg IV + docetaxel 75 mg/m2 IV Q3W and prednisone 5 mg orally twice daily. Primary end points were PSA response rate (PSA decrease ≥50%; confirmed by a second value ≥3 weeks later), ORR per RECIST v1.1 by blinded independent central review, and safety. Key secondary end points were DCR per RECIST v1.1 (CR+PR+SD or non-CR/non-PD ≥6 mo), DOR per RECIST v1.1, radiographic PFS (rPFS) per PCWG-modified RECIST, and OS. Biospecimens (blood, tissue) were collected for biomarker analysis, including tissue PD-L1 expression, androgen receptor variant 7 (AR-v7) expression in circulating tumor cells, and a T-cell-inflamed gene expression profile (GEP). Results: Of 105 enrolled pts, 104 were treated, and 50% had measurable disease. Median (range) time from enrollment to data cutoff was 19.9 mo (1.4-27.8) for all pts and 21.8 mo (17.9-27.8) for pts with ≥27 wks follow-up (n=72). Confirmed PSA response rate was 28% in 103 pts with a baseline PSA assessment. Median time to PSA progression was 6.2 mo (95% CI, 3.7-7.4). In pts with measurable disease and ≥27 wks follow-up (n=39), ORR was 18% (7/39, all PRs) and DCR was 51%. Median DOR was 6.7 mo (range, 3.4-9.0+ [+ indicates ongoing responder]); 5 pts had a response for ≥6 mo. In all pts, median rPFS was 8.3 mo (95% CI, 7.6-10.1) and OS was 20.4 mo (16.9-NR). At 6 mo, the rPFS rate was 72.8% and OS rate was 95.3%. Treatment-related AEs (TRAEs) occurred in 96% of all pts; most frequent were alopecia (39%), diarrhea (38%), and fatigue (38%). Grade 3-5 TRAEs occurred in 40% of pts; 2 pts died of TRAEs (pneumonitis). Overall, 24% of pts were PD-L1+ (combined positive score ≥1). Of 57 pts with AR-v7 data, 17.5% were AR-v7+, 77% were AR-v7−, and 5% were undetermined. GEP was not significantly associated with ORR or PSA response. Conclusions: Pembro + docetaxel and prednisone showed activity in pts with abi or enza-pretreated mCRPC. Safety of the combination was consistent with the known profiles of the individual agents. A phase 3 study of this combination is ongoing (KEYNOTE-921, NCT03834506). Clinical trial information: NCT02861573 .

Targeting the Interplay of Independent Cellular Pathways and Immunity: A Challenge in Cancer Immunotherapy

“…Cohort B of the phase Ib/II KEYNOTE-365 trial analyzed the combination of docetaxel and pembrolizumab in 104 patients with the same characteristics. ORR was 18%, PSA RR was 28%, rPFS was 8.3 months, and OS was 20.4 months [103].…”

Immunotherapy in Advanced Prostate Cancer: Current Knowledge and Future Directions

“…Cohort B of the phase Ib/II KEYNOTE-365 trial analyzed the combination of docetaxel and pembrolizumab in 104 patients of the same characteristics. ORR was 18%, PSA RR was 28%, rPFS was 8.3 months, and OS was 20.4 months [77].…”

Evolving Role of Immunotherapy in Metastatic Castration Refractory Prostate Cancer

“…Cohort B of the phase Ib/II KEYNOTE 365 study evaluated the efficacy of the pembrolizumab with docetaxel combination in patients with mCRPC who had progression or were intolerant to NHT. The primary endpoints were safety, PSA response rate, and ORR [ 71 ]. Among the 104 treated patients, the PSA response rate was 28%, ORR was 18%, and DCR was 51%.…”

“…The most common treatment-related AEs (≥ 30%) were alopecia, diarrhea, and fatigue. Again, T-cell-inflamed gene expression profile was not associated with ORR or PSA response [ 71 ]. The combination is currently being evaluated in the phase III KEYNOTE 921 (NCT03834506) trial, with a projected study completion in 2023 [ 71 ].…”