Table 3 Representative clinical trials using bispecific antibodies to treat NSCLC

MARIPOSA

Treatment-naïve EGFR-mutant advanced NSCLC

Lazertinib + amivantamab

Osimertinib

86

85

23.7

16.6

0.70 [0.58–0.85]

^$74%

^$69%

0.80 [0.61–1.05]

75

43

[17]

CHRYSALIS

Osimertinib-resistant EGFR-mutant advanced NSCLC (combinational cohort)

Lazertinib + amivantamab

36

4.9

4

[138, 144]

Advanced NSCLC with EGFR exon 20 insertion (cohort D)

Amivantamab

39

8.3

35

Advanced NSCLC with MET exon 14 skipping (cohort MET-2)

Amivantamab

33

5.4

15.8

42

CHRYSALIS-2

Advanced NSCLC with uncommon EGFR mutations (cohort C)

[142]

 Total population

Lazertinib + amivantamab

52

11

 Treatment-naïve

Lazertinib + amivantamab

57

19.5

 TKI-pretreated

Lazertinib + amivantamab

48

7.8

PAPILLON

Treatment-naïve advanced NSCLC with EGFR exon 20 insertion

Amivantamab + CT

CT

73

47

11.4

6.7

0.40 [0.30–0.53]

NR

24.4

0.67 [0.42–1.09]

75

54

[139]

PALMOMA-3

Osimertinib- and chemotherapy-pretreated EGFR-mutant advanced NSCLC

Lazertinib + amivantamab (s.c.)

Lazertinib + amivantamab (i.v.)

27

27

6.1

4.3

0.84 [0.64–1.10]

NR

NR

0.62 [0.42–0.92]

52

56

[143]

HARMONi-a

Osimertinib-pretreated EGFR-mutant advanced NSCLC

Ivonescimab + CT

CT

50.6

35.4

7.1

4.8

0.46 [0.34–0.62]

61.5

49.1

[20]

HARMONi-2

Advanced NSCLC with PD-L1 ≥ 50%

Ivonescimab

Pembrolizumab

50

38.5

11.14

5.82

0.51 [0.38–0.69]

29.4

15.6

[152]

First-in-human study of MEDI5752

Advanced non-squamous NSCLC

[155]

 Randomized cohort

MEDI5752 1500 mg + CT

50

15.1

NR

80

 Randomized cohort

Pembrolizumab + CT

47.6

8.9

16.5

61

 Single-arm cohort

MEDI5752 750 mg + CT

40.8

50

Advanced non-squamous NSCLC with PD-L1 < 1%

 Randomized cohort

MEDI5752 1500 mg + CT

55.6

13.4

 Randomized cohort

Pembrolizumab + CT

30

9.0

 Single-arm cohort

MEDI5752 750 mg + CT

48

AK104-202

CT-pretreated advanced NSCLC

[156]

 ICI-naïve

Cadonilimab (AK104)

10

1.97

19.61

10

 Primary resistance to IO

Cadonilimab (AK104)

0

1.87

4.93

0

 Acquired resistance to IO

Cadonilimab (AK104)

0

1.84

13.16

18.8

KN046-201

cohort A and B

Advanced NSCLC

[158,159,160]

 Cohort A/B: Resistance to CT

KN046

14.1

3.7

19.8

42.2

 *Cohort C: Resistance to IO

KN046

3.2

2.8

13.3

22.6

 Cohort D: Resistance to TKI

KN046

26.9

5.52

12.68

53.8

KN406-202

Treatment-naïve advanced NSCLC

KN046 + CT

46

5.8

26.6

66.7

[161]