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Table 1 Summary of ATR inhibitor-based clinical trials

From: Ataxia telangiectasia and Rad3-related inhibitors and cancer therapy: where we stand

ATRi Target cancer type Treatment Phase Biomarker selection Efficacy and toxicity Identifier
M6620 (formerly VX-970, IV) Advanced solid tumor Alone or with carboplatin/paclitaxel I   Gr 3/4: 5–21% 1 pt had PR NCT03309150
Advanced solid tumor Gemcitabine, cisplatin, etoposide, or carboplatin I TP53 mutation of ATM loss Gem, Gr 3/4, 50%; PFS, 8.0–29.3 weeks
Cis, Gr 3/4, 46%; PFS, 4.1 months
Advanced solid tumor Irinotecan I    NCT02595931
Small-cell cancers Topotecan I/II DDR pathway mutations Gr 3/4, 10–19%; PR + SD, 42.8% NCT02487095
Urothelial carcinoma Cisplatin or gemcitabine I/II p53, p21, and ERCC2 mutations   NCT02567409
Ovarian cancer Carboplatin + gemcitabine I/II DNA damage assay, HRR mutations   NCT02627443
Ovarian cancer Gemcitabine II    NCT02595892
mCRPC Carboplatin ± docetaxel II    NCT03517969
Advanced solid tumor Cisplatin + veliparib I DNA damage and apoptotic assay Gr 3/4, 4–31%; 3 pts had PR NCT02723864
HNSCC Cisplatin + XRT I DNA damage assay   NCT02567422
Brain metastases Whole brain XRT I ATR, CHK1, RAD51, cyclin E, DNA-PK assay   NCT02589522
M4344 (oral) Advanced solid tumor Carboplatin, gemcitabine, or cisplatin I    NCT02278250
AZD6738 (oral) CLL, PLL or B-cell lymphoma Alone I ATR targeted inhibition biomarker   NCT01955668
HNSCC Alone I TH1/IFNγ gene and TIL state   NCT03022409
Refractory CLL Acalabrutinib I    NCT03328273
Advanced solid tumor Paclitaxel I    NCT02630199
Advanced solid tumor Carboplatin, olaparib, or durvalumab I/II ATM deficiency Carbo, Gr 3/4, 27–33%; 3 pts had PR
Ola, Gr 3/4, 4–7%; 2 pts BRCA-mut had PR
Dur, no Gr 3/4; 1 pt had PR, 1 had CR
TNBC Olaparib II HRR mutations   NCT03330847
Advanced tumor Olaparib II    NCT02576444
SCLC Olaparib II    NCT03428607
Ovarian cancer Olaparib II    NCT03462342
NSCLC Durvalumab II    NCT03334617
Advanced solid tumor XRT I    NCT02223923
BAY1895344 Solid tumor and lymphoma Alone I    NCT03188965
  1. Abbreviations: CLL chronic lymphocytic leukemia, DDR DNA damage response, Gr grade, HNSCC head and neck squamous cell carcinoma, HRR homologous recombination repair, mCRPC metastatic castration-resistant prostate cancer, NSCLC non–small cell lung cancer, PFS progression-free survival, PLL prolymphocytic leukemia, PR partial response, SCLC small cell lung cancer, SD stable disease, TNBC triple-negative breast cancer, XRT X-ray radiotherapy