Table 1.
Ongoing clinical trials of combination DNA targeting and/or immunotherapy agents in TNBC or BC with DDR mutations.
| Phase | Trial ID | BC subtype | Biomarkers | Regimen | Targets | Clinical endpoint |
|---|---|---|---|---|---|---|
| I | NCT03544125 | mTNBC | Pre- and post-tumor biopsy (CLIA) analytics | Olaparib + Durvalumab | PARP PD-L1 |
Safety, ORR, DOR, PFS, OS |
| I | NCT03101280 | Advanced or mTNBC | – | Rucaparib + Atezolizumab | PARP PD-L1 |
DLTs, PK, ORR, CR, PFS |
| I/II |
NCT03964532 TALAVE |
Advanced BC | Germline BRCA1/2 Deleterious mutation OR BRCA1/2 wild status TNBC; Serial biopsies for PD-L1 |
Talazoparib + Avelumab | PARP PD-L1 |
Safety, ORR, PFS, OS |
| II | NCT04584255 | BRCAm Stage I-III BC |
BRCA mutations, pre- and post-TILs, STING activation, serum immune | Niraparib + Dostarlimab | PARP PD-1 |
pCR, RCB |
| II | NCT02849496 | HER- mBC | BRCA 1/2 mutation, HRD, PD-L1, TILs, ctDNA | Olaparib + Atezolizumab | PARP PD-L1 |
PFS, TTF, ORR, DOR, irBOR |
| II | NCT03801369 | mTNBC | Tumor characteristics, predictive biomarkers | Olaparib + Durvalumab | PARP PD-L1 |
ORR, OS |
| II | NCT03025035 | Advanced BRCAm BC | germline mutations in BRCA1 or BRCA2 | Olaparib + Pembrolizumab | PARP PD-1 |
ORR, PFS, OS, irRECIST |
| II |
NCT03167619 DORA |
Advanced or mTNBC | Molecular biomarkers, TILs, PD-L1 status, cTC, plasma DNA | Olaparib + Durvalumab | PARP PD-L1 |
PFS, CR, PR, SD, OS |
| II/III |
NCT04191135 KEYLYNK-009 |
Advanced TNBC | - | Olaparib + Pembrolizumab | PARP PD-1 |
PFS, OS |
| I/II |
NCT03594396 MEDIOLA |
Stage II/III TNBC | Serial tumor and serum biopsy study | Olaparib + Durvalumab | PARP PD-L1 |
pCR, ORR |
| I/II | NCT02484404 | Advanced or mTNBC | gBRCAm status | Olaparib + Durvalumab | PARP PD-L1 |
Safety, ORR, PFS |
| I/II |
NCT02657889 TOPACIO |
Advanced or mTNBC | – | Niraparib + Pembrolizumab | PARP PD-1 |
DLTs, ORR, DOR, PFS, OS, PK |
| II |
NCT04169841 GUIDE2REPAIR |
HR-mutated advanced or metastatic BC | HR repair gene mutations | Olaparib + Durvalumab + Tremelimumab | PARP PD-L1 CTLA-4 |
Safety, PFS |
| II | NCT03330847 | mTNBC | BRCA1/2 mutations or HRRm | Olaparib + Ceralasertib or Adavosertib |
PARP ATR WEE1 |
PFS, ORR, OS, DOR, PK |
| I | NCT03945604 | Advanced or mTNBC | - | Apatinib + Fluzoparib + Camrelizumab | VEGF PARP PD-1 |
DLT, ORR, PFS, OS |
| II |
NCT04837209 NADiR |
mTNBC | TILs, ctDNA | Niraparib + Dostarlimab + RT |
PARP PD-1 DNAx |
ORR, irRECIST, OS, PFS |
| I/II | NCT02264678 | Her2- BC with BRCAm or TNBC | BRCA mutations HRRm ATR inhibition, ctDNA, CTCs |
Ceralasertib + Durvalumab | ATR PD-L1 DNAx |
Safety, PK, ORR, PFS, OS |
| I | NCT01618357 | Stage II-IV BC, residual after NAC | Apoptosis/proliferation biomarkers | Pre-operative Veliparib + RT |
PARP DNAx |
Safety, MTD |
| I |
NCT03945721 UNITY |
Non-mTNBC | HRD status | Niraparib + post-op RT | PARP DNAx |
MTD, LRR, DFS, cosmesis |
| I | NCT02227082 | Advanced or mTNBC | – | Olaparib + RT | PARP DNAx |
Toxicity |
| I | NCT03542175 | Post-op TNBC | - | Rucaparib + RT | PARP DNAx |
MTD |
| I | NCT04052555 | Non-mTNBC | DDR mutations | Berzosertib + RT | ATR DNAx |
MTD, DFS, OS |
| I |
NCT02977468 Pembro/IORT |
Treatment naïve TNBC | TILs | Pembrolizumab + intra-op RT | PD-L1 DNAx |
- |
| II |
NCT03464942 AZTEC |
Advanced TNBC | – | Atezolizumab + stereotactic RT | PD-L1 DNAx |
PFS, ORR, DOR, OS |
| I | NCT02826434 | Stage II/III TNBC, HLA-A2+ |
Immune response rate, vaccine-specific CTLs | Peptide vaccine + Durvalumab | XBP1,CD138 PD-L1 |
Safety, tolerability |
mTNBC, Metastatic triple-negative breast cancer; BC, breast cancer; (CLIA) analytics, Proportion of completion of Clinical Laboratory Improvement Act; ORR, objective response rate; DOR, duration of response; PFS, progression-free survival; OS, overall survival; DLTs, Dose-Limiting Toxicities; MTD, maximum tolerated dose; PK, Pharmacokinetics; pCR, pathologic complete response; TILs, tumor infiltrating lymphocytes; STING, stimulator of interferon genes; RCB, pathway, residual cancer burden; HRD, homologous recombination deficiencies; HRRm, HRR-related gene mutation; ctDNA, circulating tumor DNA; TTF, time to treatment failure; irBOR, immune-related best overall response; irRECIST, immune-related; cTC, circulating tumor cells; SD, stable disease; gBRCAm, germline BRCA1 and BRCA2 mutation; DDR, DNA-damage response; DCR, pathway, disease control rate; LRR, locoregional relapse; DFS, distant relapse; CTLs, Cytotoxic T Lymphocytes; DNAx, therapeutic targeting of DNA DSBs; (HLA)-A2+, Human Leukocyte Antigen.