Skip to main content

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
NCT02157792
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
NCT02264678
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