Keynote-365 cohort a: Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).

145Background: Activity with pembro or olaparib has been observed in mCRPC pts who progressed on 2nd-generation hormonal therapy (HT) and chemotherapy. From KEYNOTE-365 (NCT02861573), a phase 1b/2 umbrella study testing combinations in mCRPC, we report early results from cohort A combining pembro + olaparib. Methods: Pts with mCRPC were eligible if they progressed within 6 months prior to screening determined by either PSA progression or radiologic progression in bone or soft tissue. Pts were docetaxel-pretreated for mCRPC, may have received 1 other chemotherapy, and had ≤2 2nd-generation HT. Pts received pembro 200 mg IV Q3W + olaparib 400 mg orally twice daily. Primary end points: safety and PSA response rate (confirmed PSA decline ≥50%). Key secondary end points: ORR RECIST v1.1 (investigator review), disease control rate (DCR: CR+PR+SD ≥6 mo), time to PSA progression, composite response rate (ORR RECIST v1.1, confirmed PSA response, or confirmed decrease in circulating tumor cell count from ≥5 to <5 cells/7.5 mL blood), rPFS, and OS. Results: Median follow-up was 11 mo. 41 initiated treatment (median age 69 years; PD-L1+ 27%; visceral disease 42%; RECIST-measurable 68%; homologous recombination repair mutation [HRR] 0%). See efficacy in table below. Treatment-related AEs occurred in 39 (95%) pts. Most frequent (≥30%) were anemia (37%), fatigue (34%), and nausea (34%). Grade 3-5 treatment-related AEs were in 21 (51%) pts. There were 2 deaths; only 1 was treatment-related (cause unknown). Conclusions: Combination of pembro + olaparib has activity in pts previously treated with docetaxel and ≤2 2nd-generation HT for mCRPC and who are HRR wild type. Observed safety profile for the combination is consistent with individual profiles of pembro and olaparib. Clinical trial information: NCT02861573.PSA response, pts w/elevated PSA at baseline, n/N (%)5/39 (13)ORR RECIST v1.1, pts w/measurable disease, n/N (%)2/28 (7); 2 PRsDCR, n/N (%)Measurable disease9/28 (32)Nonmeasurable disease3/13 (23)Total12/41 (29)Composite response rate, n/N (%)6/41 (15)Median (95% CI) time to confirmed PSA progression, wk16 (14, 21)Median (95% CI) rPFS per PCWG-modified RECIST, mo5 (4, 8)Median (95% CI) OS, mo14 (8, NR)