Table 1 Registered clinical trials of drugs targeting replicative stress response machinery in cancers

ATR

M6620 (VX-970)

NCT03641547/NCT02157792/NCT02723864

Phase I

Solid Tumors

with convential chemotherapies or with PARPi and cisplatin

NCT02487095

Phase I/II

Small Cell Lung Cancers

with Topotecan

NCT03896503/NCT02595892

Phase II

Small Cell Lung Cancers/ Ovarian or Fallopian Cancers

with Topotecan or Gemcitabine

VX-970

NCT02723864

Phase I

Refractory Solid Tumors

with PARPi

M4344

NCT04655183

Phase I/II

Breast Cancers (with DDR mutations)

with PARPi

M1774

NCT05986071

Phase I/II

Breast Cancers (HR+ and HER2-)

with Fulverstrant

AZD6738(Ceralasctib)

NCT02264678/NCT03022409/NCT02223923/ NCT03328273

Phase I

Solid Tumors and Chronic Lymphocytic Leukemia

with Acalabrutinib or PARPi or PARPI with Carboplatin

NCT03682289/NCT0342342/NCT03787680/ NCT04065269/NCT03330847

Phase II

Solid Tumors

with PARPi or WEE1i and PARPi

BAY1895344 (Elimusertib)

NCT04535401/NCT04491942/NCT03188965/ NCT04576091/NCT04616534/NCT04267939

Phase I

Solid Tumors

with convential chemotherapy or pembrolizumab (anti-PD-1) or PARPi

RP-3500 (Camonsertib)

NCT04972110/NCT04497116

Phase I/II

Solid Tumors

with PARPi

M1774 (tuvusertib)

NCT05396833/NCT06337630

Phase I

Solid tumors

with ATMi (Lartesertib) or Avelumab (anti-PD-L1) or Topo1i (PLX038)

NCT05882734

Phase I/II

Non-Small Cell Lung Cancers

with Cemiplimab (anti-PD-1)

NCT06424717/NCT05947500/NCT06518564

Phase II

Urothelial Cancers/Merkel Cell Skin Cancers/ Endometrial Cancers (ARID1A mutated)

with Avelumab (anti-PD-L1)

NCT06433219

Phase II

Ovarian Cancers

with ATMi (M4076, artesertib) and PARPi

berzosertib

NCT05246111

Phase I

Solid Tumors

with Topotecan

NCT04802174

Phase I/II

Small Cell Lung Cancers/ Neuroendocrine Cancers

with Lurbinectedin

ATG-018

NCT05338346

PhaseI

Solid Tumors and Hematological Malignancies

M4344

NCT04149145

PhaseI

Ovarian cancers

with PARPi

ART0380

NCT04657068

Phase I/II

Solid Tumors

with Gemcitabine and Irinotecan

IMP9064

NCT05269316

Phase I/II

Solid Tumors

ATM

AZD0156

NCT02588105^131,132

Phase I

Solid Tumors

with conventional chemotherapies or with PARPi

WSD0628

NCT05917145¹³³

Phase I

Brain Tumors

AZD1390

NCT05182905

Phase 0/Ib

Glioma

NCT04550104/NCT05678010/NCT05116254/ NCT03423628/NCT06894979

Phase I

Solid Tumors

with Radiotherapy or Radiotherapy and Durvlaumab

M3541

NCT03225105¹³⁴

Phase I

Solid Tumors

with Radiotherapy

M4076

NCT04882917¹³⁵

Phase I

Solid Tumors

KU-60019

NCT03571438

Renal Tumors

with CK2i

AZD0156

NCT02588105

Phase I

Solid Tumors

with PARPi or Irinotecan or Fluoruoracil or Folinic acid

CHK1

SCH900776

NCT01870596

Phase II

Acute Myeloid Leukemia

with Cytarabine

LY2880070

NCT05275426

Phase II

Ewing sarcoma/Desmoplastic Small Round Cell Tumors

with Gemcitamine

LY26066368 (Prexasertib)

NCT04023669/NCT02808650/NCT03495323/ NCT03735446/NCT03057145

Phase I

Solid Tumors/Acute Myeloid Leukemia

with conventional chemotherapies or PARPi

NCT02203513/NCT02873975

Phase II

Solid Tumors

PEP07

NCT05983523/NCT05659732

Phase I

Solid Tumors

SRA737

NCT02797964/NCT02797977

Phase I/II

Solid Tumors

with conventional chemotherapies

Target

Drug

Clinical trial ID (refs)

Stage

Cancer

Combination

PolQ

ART4245

NCT04991480

Phase I/II

Solid Tumors

with PARPi

GSK4524101

NCT06077877

Phase I/II

Solid Tumors

with PARPi

ART6043

NCT05898399

Phase I/II

Solid Tumors

with PARPi

Novobiocin

NCT05687110

Phase I

Solid Tumors (with DDR mutations)

ART4215

NCT04991480

Phase I/II

Breast cancers (BRCA-deficient)

with PARPi

Rad51

CYT-0851

NCT03997968¹³⁶

Phase I/II

B-cell malignancies and Solid Tumors

with conventional chemotherapies or Rituximab and bendamustine

Wee1

ZN-c3 (Azenosertib)

NCT05368506

Phase I

Breast Cancers (TNBCs) and Ovarian Cancers

NCT05198804/NCT05682170

Phase I/II

Ovarian cancers (Platinum resistant)/AML

with PARPi or BCL-2i

NCT06015659/NCT04814108/NCT05128825

Phase II

Pancreatic Cancers/Uterine serous carcinoma/Ovarian cancers (Platinum resistant), Fallopian Tube or Primary Peritoneal Cancers

with Gemcitabine

AZD1775 (MK-1775, Adavosertib)

NCT02617277/NCT01748825/NCT00648648/ NCT02508246/NCT02791919/NCT03028766/ NCT02381548/NCT03345784

Phase I

Solid Tumors and Acute Myeloid Leukemia

with conventional chemotherapies or Belinostat

NCT02194829

Phase I/II

Pancreatic Cancers

with Paclitaxel or Gemcitabine

NCT02037230

Phase I/II

Pancreatic Cancers

with Gemcitabine and Radiotherapy

NCT02906059

Phase Ib

Cololorectal Cancers

with Irinotecan

NCT01164995/NCT02272790/NCT02101775/ NCT01357161/NCT02448329/NCT02196168/ NCT02666950/NCT03253679/NCT03012477/ NCT03668340/NCT03718143^137,138

Phase II

Solid Tumors and Acute Myeloid Leukemia

with conventional chemotherapies

SY-4835

NCT05291182

Phase I

Solid Tumors

DNA-PK

AZD7648

NCT03907969¹³⁹

Phase I/IIa

Solid Tumors

with doxorubicin

CC-115

NCT01353625¹⁴⁰

Phase I

Solid Tumors and Hematological Malignancies

with mTORi

BY101298

NCT06524804

Phase Ib/II

Solid Tumors

with Radiotherapy

M3814 (peposertib)

NCT02316197/NCT05711615/NCT05687136

Phase I

Solid Tumors and Chronic Lymphocytic Leukemia

with doxorubicin or ATRi

NCT02516813

Phase Ia/Ib

Solid Tumors

with Radiotherapy

NCT04172532/NCT04071236

Phase I/II

Pancreatic cancers/Prostate Cancers

with Radiotherapy