Table 3 Clinical trials of ADCs in HER2-positive advanced G/GEJ adenocarcinoma

T-DM1

GATSBY

2017 [68]

II/III

terminated

Second-line

HER2-positive advanced GC

Docetaxel + Paclitaxel

T-DM1 2.4 mg/kg

T-DM1 3.6 mg/kg

37

75

70

mOS 8.6 m(P = 0.86)

8.6 m

7.9 m

Grade ≥ 3 70%

60%

DS-8201

Kohei Shitara 2019 [74]

I

processing

Second-line and beyond

HER2-positive advanced G/GEJ adenocarcinoma

DS-8201

44

ORR 43.2%

Grade ≥ 3 Anemia 30%

Nneutropenia 20%

Kohei Shitara 2020 [24]

II

Completed

Third-line and beyond

HER2-positive advanced G/GEJ adenocarcinoma

DS-8201

Chemotherapy (Irinotecan/Paclitaxel)

125

62(55/7)

ORR 51%(P<0.001)

14%

mOS 12.5 m(P = 0.01)

8.4 m

Grade ≥ 3 Neutropenia 51%

24%

Anemia 38%

23%

Disitamab vedotin

Yingying Xu 2021 [76]

I

Completed

HER2-overexpressing locally advanced/metastatic solid tumors

Disitamab vedotin

57

ORR 21.0%

DCR 49.1%

Grade ≥ 3 Neutropenia 19.3%

Leukopenia 17.5%

Zhi Peng 2021 [77]

II

Completed

Third-line and beyond

HER2-overexpressing advanced G/GEJ adenocarcinoma

Disitamab vedotin

125

mOS 7.9 m

mPFS 4.1 m

Leukopenia 53.6%

Fatigue 53.6%

ARX788

ACE-Gastric-01

2021 [80]

I

processing

HER2-positive advanced G/GEJ adenocarcinoma

ARX788

23

ORR 45.5%

DCR 50.0%

Grade ≥ 3 26.1%

MEDI4276

Mark D. Pegram 2021 [84]

I

Completed

Second-line and beyond

HER2-positive BC, GC

MEDI4726

47(32/15)

GC mPFS 1.8 m

mOS 6.5 m

Grade 3/4 AST elevation 21.3%

SYD985

NCT02277717

2019 [81]

I

Completed

HER2 1+ or higher solid tumors

SYD985

dose escalation 39

dose expansion 146

GC ORR 6%

dose escalation Grade 3/4 keratitis 3

Fatigue 2

dose expansion Fatigue 33%

conjunctivitis 31%

A166

NCT03602079

2020 [82]

I-II

processing

Second-line and beyond

HER2-positive locally advanced/metastatic solid tumors

A166

35

stable disease 33%

part response 26%

DCR 59%

≥10% Keratitis, decreased appetite, xerophthalmia, blurred vision