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. Author manuscript; available in PMC: 2022 Oct 1.
Published in final edited form as: Trends Cancer. 2021 Jun 30;7(10):930–957. doi: 10.1016/j.trecan.2021.06.002

Table 2.

Combination strategies of immune checkpoint blockade with RSR-targeting drugs.a

Drug Phase Study population Biomarker Treatment Efficacy Safety Reference
Berzosertib (M6620; VX-970) I Advanced solid tumors that are DDR deficient; N=36 Mutations suggestive of DDR deficiency including ARID1A, ATM, ATR, ATRX, BAP1, BARD1, BRCA1/2, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, MSH2, NBN (NBS1), PALB2, RAD51, RAD51C, RAD51D, SMARCB1, VHL

  • Avelumab (D1, D15) + berzosertib (D1, D,8, D15, D22) q28 days

 Recruitment ongoing N/A NCT04266912
II Recurrent platinum-sensitive ovarian cancer, that is resistant to PARPi; N= 90 N/A

  • Part A: Safety run-in of carboplatin AUC 5 (D1) + avelumab 1600mg (D1) + berzosertib 90mg/m2 (D2) q21 days

  • Part B: chemotherapy (carboplatin + paclitaxel/gemcitabine/PLD) +/− bevacizumab → bevacizumab maintenance; versus carboplatin + avelumab + berzosertib for 6 cycles → avelumab maintenance

 Recruitment ongoing N/A NCT03704467
Ceralasertib (AZD6738) II Advanced NSCLC who have progressed on immunotherapy; N=410 Subjects with ATM loss were assigned to ceralasertib + durvalumab

  • Novel durvalumab combinations including ceralasertib 240 mg BD (D1–14) + durvalumab 1500mg (D1), q28 days

  • ORR: 8.3%

  • Median PFS: 7.43 months (95% CI, 3.45–9.46)

  • Median OS:15.80 months (95% CI, 11.01-NR)

 N/A NCT03334617
II Advanced biliary tract cancers who have previously received immunotherapy; N=26 N/A

  • Ceralasertib 240 mg BD (D15–28) + durvalumab 1500mg (D1), q28days

 Recruitment ongoing N/A NCT04298008
II Advanced NSCLC who have progressed on immunotherapy; N=120 N/A

  • Novel durvalumab combinations compared against docetaxel chemotherapy. Including ceralasertib 240 mg BD (D1–7 for cycle 1, D22–28 for subsequent cycles) + durvalumab 1500mg (D1), q28 days

 Recruitment ongoing N/A NCT03833440
Elimusertib (BAY1895344) Ib/II Advanced solid tumors; N = 110 DDR deficiency biomarker positive, including ATM deleterious mutation

  • Elimusertib + pembrolizumab

 Recruitment ongoing N/A NCT04095273
I Recurrent HNSCC; N= 38 N/A

  • Elimusertib + pembrolizumab + SBRT

 Not yet recruiting N/A NCT04576091
Prexasertib I Advanced solid tumors; N=17 N/A

  • Prexasertib + LY3300054 (novel PD-L1 inhibitor).

 Active, not recruiting N/A NCT03495323
Peposertib (Nedisertib; M3814) I Advanced solid tumors; N=47 N/A

  • Peposertib + avelumab +/− palliative RT

 Recruitment ongoing N/A NCT03724890
I/II Metastatic castration resistant prostate cancer; N =24 N/A

  • Radium-223 (D1)

  • Radium-223 (D1) + peposertib OD/BD (D3–26) q28 days × 6 cycles

  • Radium-223 (D1) + peposertib OD/BD (D3–26) + avelumab (D1, D15) q28 days × 6 cycles

 Recruitment ongoing N/A NCT04071236
I/II Advanced solid tumors and hepatobiliary cancers; N=92 N/A

  • Hypo fractionated RT (D-17 to D-7) + avelumab (D1,D15) q28 days

  • Hypo fractionated RT (D-17 to D-7) + peposertib OD (D1–28) + avelumab (D1,D15) q28 days

 Recruitment ongoing N/A NCT04068194
ZN-c3 I/II Advanced solid tumors; N=360 N/A

  • ZN-c3 monotherapy in escalating doses followed by dose-expansion

  • ZN-c3 + talazoparib

  • ZN-c3 + pembrolizumab

 Recruitment ongoing N/A NCT04158336
Adavosertib I Advanced solid tumors; N=54 N/A

  • Cohort A: adavosertib 125 mg BD (D1–5, 15–19) + durvalumab 1500mg (D1) q28days

  • Cohort B: adavosertib 125–175 mg BD (D15–17, 22–24) + durvalumab 1500mg (D1) q28days

  • Cohort C: adavosertib 125 mg BD (D8–10, 15–17, 22–24) + durvalumab 1500mg (D1) q28days

  • Cohort D: adavosertib 200–300 mg (D15–19, D22–26) ) + durvalumab 1500mg (D1) q28days

  • MTD/RP2D: adavosertib 150mg BD (D15–17, 22–24) + durvalumab 1500mg (D1) q28 days

  • Overall DCR: 36%

  • Grade≥3 AEs 43–86%, most commonly fatigue (15%), diarrhea (11%), nausea (9%)

  • 13% of patients had adavosertib-related SAEs including drug-induced liver injury

 NCT02617277
a

Abbreviations: AE, adverse events; AUC, area under curve; CI, confidence interval; DCR, disease control rate; DDR, DNA damage response; HNSCC, head and neck squamous cell carcinoma; MTD, maximum tolerated dose; NR, not reached; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; RP2D, recommended phase II dose; RT, radiotherapy; SAE, serious adverse events.