Table 4 Representative clinical trials using ADCs to treat patients with NSCLC

Destiny-Lung01

Previously treated HER2-mutant advanced NSCLC

Traztuzumab deruxtecan

55

8.2

17.8

46

[164]

Destiny-Lung02

Previously treated HER2-mutant advanced NSCLC

Traztuzumab deruxtecan 5.4 mg/kg

49

9.9

19.5

38.6

[165]

Traztuzumab deruxtecan 6.4 mg/kg

56

15.4

NE

TROPION-PanTumor01

Previously treated advanced solid tumor

[168,169,170]

 NSCLC cohort

Datopotamab deruxtecan 4 mg/kg

Datopotamab deruxtecan 6 mg/kg

Datopotamab deruxtecan 8 mg/kg

22

26

23.8

4.3

6.9

5.2

12.9

11.4

10.5

30

54

58.8

Subgroup with AGA

Datopotamab deruxtecan

35

TROPION-Lung05

Previously treated advanced NSCLC with actional driver alterations

[171, 172]

 Total population

 EGFR mutation

 ALK rearrangement

 Brain metastasis

Datopotamab deruxtecan

Datopotamab deruxtecan

Datopotamab deruxtecan

Datopotamab deruxtecan

49

34

8

^$22

5.4

5.8

4.3

47

TROPION-Lung01

Previously treated advanced NSCLC

Datopotamab deruxtecan

Docetaxel

4.4

3.7

0.75 [0.62–0.91]

12.4

11.0

0.90 [0.72–1.13]

25

41

[173]

TROPION-Lung02

Advanced NSCLC with ≤ 2 prior lines of therapy

[175]

 Total population

Datopotamab deruxtecan + ICI

Datopotamab deruxtecan + ICI + CT

38

49

31

58

 First-line

Datopotamab deruxtecan + ICI

Datopotamab deruxtecan + ICI + CT

50

57

TROPION-Lung04

Treatment-naïve advanced NSCLC without actional driver alterations

Datopotamab deruxtecan + ICI

Datopotamab deruxtecan + ICI + CT

50

76.9

31.6

57.1

[176]

IMMU-132–01

Previously treated advanced NSCLC

Sacituzumab govitecan

17

5.2

9.5

[177]

EVOKE-02

Treatment-naïve advanced NSCLC

[178]

 PD-L1 ≥ 50% (cohort A)

 PD-L1 < 50% (cohort B)

Sacituzumab govitecan

Sacituzumab govitecan

67

44

13.1

40

EVOKE-01

Advanced NSCLC with acquired resistance to anti-PD1

Sacituzumab govitecan

Docetaxel

13.7

18.1

4.1

3.9

0.92 [0.77–1.11]

11.1

8.9

0.84 [0.68–1.04]

66.6

75.7

[179]

Phase 2 study of sacituzumab tirumotecan

Previously treated advanced NSCLC

[181]

 Total population

 EGFR-mutant

 EGFR-wild type

  Non-squamous

  Squamous

Sacituzumab tirumotecan

Sacituzumab tirumotecan

Sacituzumab tirumotecan

Sacituzumab tirumotecan

Sacituzumab tirumotecan

43.6

60.0

26.3

22.2

30.0

7.2

11.5

5.3

5.8

5.1

22.6

22.7

14.1

16.2

12.8

69.8

OptiTROP-Lung01

Treatment-naïve NSCLC

[182]

 Cohort 1A

SKB264 5 mg/kg + KL-A167 1200 mg

48.6

15.4

 Cohort 1B

  Non-squamous

  Squamous

  PD-L1 < 1%

  PD-L1 1–49%

  PD-L1 ≥ 50%

SKB264 5 mg/kg + KL-A167 900 mg

77.6

72.7

84.0

63.2

81.3

87.0

*84.6%

*93.8%

*73.5%

*82.2%

*76.6%

*91.3%

HERTHENA-Lung01

EGFR-mutant advanced NSCLC with acquired resistance to TKI and platinum-based CT

[184]

 Total population

Post 3rd generation EGFR-TKI

Patritumab deruxtecan

Patritumab deruxtecan

28.4

28.2

5.5

5.5

11.9

11.8

45.3

Phase 1/1b study of telisotuzumab vedotin

EGFR-mutant advanced NSCLC with acquired resistance to osimertinib

Osimertinib + telisotuzumab vedotin

50

7.4

32

[186, 187]

LUMINOSITY

Advanced NSCLC with ≤ 2 prior lines of therapy

[188]

 c-Met OE NSQ EGFR WT

  c-Met high

  c-Met intermediate

Telisotuzumab vedotin

Telisotuzumab vedotin

Telisotuzumab vedotin

28.6

34.6

22.9

5.7

5.5

6.0

14.5

14.6

14.2

 c-Met OE NSQ EGFR mutant

  c-Met high

  c-Met intermediate

Telisotuzumab vedotin

Telisotuzumab vedotin

Telisotuzumab vedotin

11.6

16.7

0

 c-Met OE SQ

Telisotuzumab vedotin

11.1