Table 1 The summary of phase I/II clinical trials about ovarian cancer with resistance based on mechanisms. Some novel agents in I/II-phase clinical trials attempt to reverse resistance in ovarian cancer by targeting transmembrane transport, DNA damage repair, signal pathway, and epigenetic modification. We summarized these components of clinical trials including the study identifier, phase, experiment drug, involved target, disease condition, primary outcome measures, study status, study results

Clinical trials targeting transmembrane transport

 NCT04918186

II

BA3011（BA3021） + Durvalumab

Axl （ROR2）

platinum resistant high grade serous ovarian cancer

ORR

Recruiting

NA

 NCT01335958

I

DMUC5754A

MUC16

Platinum-Resistant Ovarian Cancer

DLTs

Completed, published

Grade ≥3-related AE in ≥5%， anti-tumor activity in MUC16-high patients

 NCT02146313

I

DMUC4064A

MUC16

Platinum-Resistant Ovarian Cancer

DLTs, MTD, PR2D, AEs, sAEs

Completed published

grade ≥ 3 toxicities in 25%

RP2D: 5.2 mg/kg, CBR: 46% in MUC16-high patients

 NCT01469793

I

DMOT4039A

Mesothelin

Platinum-Resistant Ovarian Cancer

MTD, DLTs RP2D

Completed， published

RP2D： 2.4 mg/kg (q3w) and 1.0 mg/kg (q1w)； SAE:8.5%

 NCT02751918

Ib

BAY94-9343+PLD

Mesothelin

Mesothelin-expressing Platinum-resistant Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

MTD, AEs

Completed published

ORR: 27.7% (all) ORR: 42.1% (high mesothelin expression) MTD: 6.5 mg/kg

The most common AE: nausea (47.7%)

 NCT01363947

I

DNIB0600A

NaPi2b

Non-mucinous and platinum-resistant ovarian cancer

AEs, DLTs, RP2D, OR, DOR

Completed published

grade ≥3 neutropenia (10%) RP2D: 2.4 mg/kg(q3w）

All RECIST responses (NaPi2b-high)

 NCT04504916

II

Zilovertamab Vedotin

ROR1

platinum-resistant ovarian cancer

ORR, TTR, DOR, PFS, OS

Completed

NA

 NCT02539719

1a/1b

Tamrintamab pamozirine

DPEP3

platinum-resistant/refractory ovarian cancer

AEs, ORR

Completed published

ORR:4% (intolerable) Higher response in higher DPEP3

Clinical trials targeting DDR

 NCT02595892

II

Gemcitabine Hydrochloride + M6620

ATR

recurrent, platinum-resistant high-grade serous ovarian cancer

PFS, ORR

Completed published

Show some benefits of adding M6620 to gemcitabine (PFS: 22.9w vs 14.7w)

 NCT04149145

I

M4344+Niraparib

ATR

PARPi-resistant advanced epithelial serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer

AEs, MTD

Not yet recruiting

NA

 NCT03462342

I

AZD6738+ Olaparib

ATR

Recurrent platinum-sensitive and platinum-resistant HGSOC

AEs, ORR, PFS

Recruiting

NA

 NCT03704467

Ib//II

Carboplatin + M6620 + Avelumab

ATR

PARPi-resistant Ovarian Cancer

DLT, AEs

Recruitment completed

NA

 NCT01164995

II

MK-1775 + carboplatin

WEE1

Refractory or Platinum Resistant Ovarian Cancer with TP53 mutation

AEs, antitumor activity (CT/CA125)

Completed published

ORR: 41%, PFS: 5.6m AE: bone marrow toxicity, nausea and vomiting

 NCT03579316

II

AZD1775+ olaparib

WEE1

PARPi-resistant ovarian cancer

ORR, safety and tolerability

Recruiting

NA

 NCT02272790

II

Adavosertib+ Carboplatin/

PLD/Paclitaxel/

Gemcitabine

WEE1

Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ORR, AEs

Completed published

ORR (overall):31.9% ORR (adavosertib+ Carboplatin):66.7% Grade ≥3 AEs: anemia (33%), neutropenia (45.7%), Thrombocytopenia (31.9%)

 NCT05198804

I/II

ZN-c3 + Niraparib

WEE1

Platinum-/PARPi-Resistant Ovarian Cancer

DLTs, PFS, ORR

Recruiting

NA

 NCT04516447

I

ZN-c3+ PLD/carboplatin/ paclitaxel/gemcitabine

WEE1

Platinum-Resistant Ovarian, Peritoneal or Fallopian Tube Cancer

AEs, MTD, RP2D

Recruiting

NA

 NCT02101775

II

Gemcitabine with or without MK-1775

WEE1

Recurrent, Platinum Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers

PFS, OR, OS, AEs

Completed published

PFS: 4.6 months vs 3.0 months (HR 0.56, 95%CI:0.35 to 0.90, p=0.015). OS: 11.5 months vs 7.2 months (HR 0.56, 95%CI 0.34 to 0.92, p=0.022). PR rate: 21% vs 3% (p=0.02)

 NCT02203513

II

LY2606368

CHK1/2

recurrent platinum-resistant HGSOC with BRCA wild-type or mutation

ORR

Partially completed (BRCA wide-type), recruitment ongoing

PR (assessable per protocol): 33% (8/24), Grade≥3AEs: neutropenia (93%); reduced white blood cell count (82%); thrombocytopenia (25%), anemia (11%).

 NCT03414047

II

LY2606368

CHK1/2

platinum-resistant HGSOC with BRCA wild-type or mutation

ORR

Completed

In platinum resistant patients: ORR (Cohorts 1--3): 12.1% DCR was 37.1%,

 NCT04678102

I

PHI-101

CHK2

Platinum Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancers

DLT, MTD

Recruiting

NA

 NCT02797964

I/II

SRA737

CHK1

Platinum-resistant or intolerant HGSOC

AEs, MTD

Completed

MTD: 1000 mg QD

RP2D: 800 mg QD

Mild toxicities

Clinical trials targeting signaling pathway

 NCT03875820

I

Defatcinib+VS-6766

MAPK

LGSOC without conventional treatment

Estabilsh tolerated dose and Measure. AEs

Active, not recruiting

NA

 NCT03648489

II

TAK228

PI3K/AKT/mTOR

platinum-resistant ovarian cancer

PFS

Active, not recruiting

NA

 NCT03586661

I

Copanlisib

PI3K/AKT

platinum-resistant ovarian cancer with BRCA mutation

MTD and RP2D

Active, not recruiting

NA

 NCT04374630

II

Afuresertib+paclitaxel

PI3K/AKT

Platinum-Resistant Ovarian Cancer

PFS

Recruiting

NA

 NCT04586335

I

CYH33

PI3K/AKT

Platinum-/PARPi-Resistant Ovarian Cancer

DLT, ORR

Recruiting

NA

 NCT04055649

II

ONC201

PI3K/AKT、MAPK

Platinum Refractory or Resistant Ovarian Cancer

AEs, DLT's, ORR, PFS

Recruiting

NA

 NCT05295589

II

Copanlisib

PI3K/AKT

Recurrent Platinum Resistant Ovarian Cancer

PFS

Not yet recruiting

NA

 NCT03363867

II

Cobimetinib

MAPK

Recurrent Platinum Resistant High Grade Serous Ovarian Cancer

ORR

Recruiting

NA

 NCT03639246

I/II

AVB-S6-500

GAS6-AXL

platinum-resistant Recurrent Ovarian Cancer

AEs

 PFS

Completed published

ORR (AVB-500 + PAC): 34.8% median DoR, PFS, and OS (AVB-500 + PAC)：7.0, 3.1, and 10.3 months, respectively RP2D (AVB-500): 15 mg/kg

 NCT04019288

I/II

AVB-S6-500

GAS6-AXL

Platinum-Resistant Ovarian cancer

AEs

Completed published

no DLTs and grade ≥3 AEs within 6-week Exploratory studies are ongoing.

 NCT04893551

I

Tilvestamab

GAS6-AXL

Platinum-resistant relapsed HGSOC

AEs

Terminated

NA

 NCT01952249

Ib

Demcizumab+paclitaxel

Notch

platinum-resistant ovarian, primary peritoneal, and fallopian tube cancer

DLTs

Completed

RP2D: 3.5mg/kg

tolerability, clinical activity,

 NCT03776812

II

Relacorilant +

Nab-Paclitaxel

GR

recurrent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer

PFS, ORR, DOR

Completed

ORR is similar among arms (35%); Intermittent arm:

OS, 13.9 months, PFS, 5.6 months Continuous arm;

OS months, 11.3, PFS, 5.3 months Nab-paclitaxel: OS, 12.2 months, PFS, 3.8 months

 NCT03319628

1/II

XMT-1536

NaPi2b

platinum-resistant ovarian cancer

MTD and RP2D

Recruiting

NA

 NCT04502602

1/1b

Niraparib + Neratinib

HER2

Platinum-resistant Ovarian Cancer

RP2D, PFS, AEs

Recruiting

NA

 NCT03287271

I/II

Defactinib (VS-6063) +Carboplatin/PaclitaxeL

FAK

Carboplatin-resistant Ovarian Cancer

ORR, AEs

Recruiting

NA

Clinical trials targeting epigenic modification

 NCT05327010

II

ZEN003694 +Talazoparib

BET bromodomain

PARPi-resistant recurrent ovarian cancer with BRCA mutation or DDR aberrations

ORR

Recruiting

NA

 NCT04840589

I

ZEN003694+nivolumab+/- Ipilimumab

BET bromodomain

Recurrent Platinum-Resistant Ovarian Carcinoma

RP2D

Recruiting

NA

 NCT03206047

I/II

atezolizumab+/-Guadecitabine+/-CDX-1401 vaccine

DNMT

platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma

AEs, PFS

Recruiting

NA

 NCT02901899

II

Guadecitabine + Pembrolizumab

DNMT

recurrent platinum resistant ovarian cancer

ORR

Complete

PR: 8.6%; SD:22.9%; CBR: 31.4% (95% CI: 16.9%-49.3%);

duration of clinical benefit was 6.8 months