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. 2023 Aug 17;30(8):7672–7691. doi: 10.3390/curroncol30080556

Table 5.

Select Clinical Trials of Olaparib/PARPi Combination Therapy in Breast Cancer and Other Solid Tumours*.

Trial Population Intervention Outcomes
Olaparib and Pembrolizumab in Breast Cancer
KEYLYNK-0072 [65]
(NCT04123366)
Phase II, single-arm, open-label study		 Previously treated advanced solid tumours with mutations in homologous recombination repair genes and/or homologous recombination deficiency (including breast cancer)
(N = 168)

  • Olaparib 300 mg BID + pembrolizumab 200 mg IV Q3W (35 cycles) until PD or unacceptable AEs

  • Grade 3/4 TRAEs, 35.7%; grade 5 TRAEs, 0

  • Discontinuations due to TRAEs, 2,4%

  • Common TRAEs: nausea, 39.3%; anemia, 30.4%; fatigue, 15.5%

  • Authors noted that “olaparib + pembrolizumab showed promising antitumour activity with manageable safety…”
TOPACIO/KEYNOTE-162 † [66]
(NCT02657889)
Phase II, single arm, open-label study		 Advanced/metastatic TNBC
(irrespective of BRCA status
or PD-L1 expression)
(N = 55)

  • Niraparib 200 mg PO daily† + pembrolizumab 200 mg IV Q3W

  • Most common grade ≥3 AEs: anemia, 18%; thrombocytopenia, 15%; fatigue, 7%

  • IRAEs: any, 15%; grade 3, 2%

  • Authors noted that the treatment showed “promising antitumour activity” and a “tolerable safety profile”
KEYLYNK-009 [64]
(NCT04191135)
Phase II/III, randomized, open-label study		 Locally recurrent inoperable or metastatic TNBC
(estimated N = 932)

  • Induction pembrolizumab + carboplatin-gemcitabine chemotherapy

  • Maintenance with:

  • -

    Pembrolizumab 200 mg Q3W + olaparib 300 mg BID; or

  • -

    Pembrolizumab + chemotherapy

  • Trial ongoing
NCT05203445 [67]
Phase II single-arm, open-label study		 Newly diagnosed TNBC or HR+/HER2- BC
(N = 23)

  • Olaparib 300 mg BID + pembrolizumab 400 mg IV Q6W (x 12 weeks) followed by chemotherapy and surgery

  • Trial ongoing
Olaparib and Pembrolizumab in Other Solid Tumours
KEYLYNK-010 [68]
(NCT03834519)
Phase III, randomized, open-label study		 mCRPC
(molecularly unselected)
(N = 793)		 Arms:

  • Pembrolizumab 200 mg IV Q3W for ≤35 cycles + olaparib 300 mg PO BID

  • Abiraterone or enzalutamide daily

  • Grade ≥3 TRAEs, 35% vs. 9%

  • Grade ≥3 IMAEs, 5% vs. 1%

  • Authors noted that “While pembrolizumab + olaparib resulted in more grade ≥3 TRAEs vs. NHA in patients with previously treated mCRPC, no new safety signals occurred… [69]”

  • “Most common AEs were anemia, nausea, fatigue, and decreased appetite [69]”
KEYNOTE-365 [70]
(NCT02861573)
Phase Ib/II, non-randomized, multicohort, open-label study (Cohort A)		 mCRPC (molecularly unselected)
(Cohort A: N = 102)		 Cohort A:

  • Pembrolizumab 200 mg IV Q3W olaparib 400 mg tab or 300 mg cap PO BID

  • Authors noted a “safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity”
ENGOT-OV43/KEYLYNK-001 [71]
(NCT03740165)
Phase III, randomized, double-blind study		 1L ovarian cancer
(BRCA non-mutated)
(N = 1367)		 Arms:

  • CbT Q3W x 5 cycles + pembrolizumab 200 mg IV Q3W x up to 35 cycles + olaparib 300 mg PO BID starting cycle 7

  • CbT Q3W x 5 cycles + pembrolizumab 200 mg IV Q3W x up to 35 cycles + placebo PO BID

  • CbT Q3W x 5 cycles + placebo IV Q3W + placebo PO BID

  • Trial ongoing
KEYLYNK-012 [72]
(NCT04380636)
Phase III, randomized, placebo- and active-controlled, double-blind study		 Unresectable stage III NSCLC
(N = 870)		 Arms:

  • Pembrolizumab + CRT followed by pembrolizumab + placebo

  • Pembrolizumab + CRT followed by pembrolizumab + olaparib

  • CRT followed by durvalumab

  • Trial ongoing
KEYLYNK-013 [73]
(NCT04624204)
Phase III, randomized, double-blind study		 Limited-stage SCLC
(N = 672)		 Arms:

  • Pembrolizumab + CRT followed by pembrolizumab + placebo

  • Pembrolizumab + CRT followed by pembrolizumab + olaparib

  • Pembrolizumab + CRT followed by placebo

  • Trial ongoing
Olaparib and Abemaciclib in Solid Tumours
NCI-2020-10084 [74]
(NCT04633239)
Phase I/Ib, open-label, dose escalation study		 Recurrent ovarian cancer
(N = 42)

  • Olaparib PO BID on days 1–28 + abemaciclib PO BID on days 8–28 of cycle 1 and days 1–28 of subsequent cycles

  • Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

  • Trial ongoing

* Based on a non-systematic search of medical literature and ClinicalTrials.gov based on the following keywords: “olaparib” or “PARP inhibitor” + “pembrolizumab”, “abemaciclib”, or “capecitabine”. † Note: Niraparib clinical trial included. AE, adverse events; BID, bis in die (twice daily); cap, capsules; CbT, carboplatin-paclitaxel; CRT, chemoradiotherapy; HRD, homologous recombination deficiency; HRRm, homologous recombination repair mutation; IMAE, immune-mediated adverse events; IRAE, immune-related adverse events; IV, intravenous; mCRPC; metastatic castration-resistant prostate cancer; NHA, next-generation hormonal agent; NSCLC, non-small cell lung cancer; PD, progressive disease; PD-L1, programmed death ligand 1; PO, per os (orally); Q3W, every 3 weeks; SCLC, small cell lunger cancer; tabs, tablets; TRAE, treatment-related adverse events; TNBC, triple-negative breast cancer.