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Table 3 Representative clinical trials using bispecific antibodies to treat NSCLC

From: Recent advances in therapeutic strategies for non-small cell lung cancer

Study

Patients

Treatment

ORR (%)

mPFS (months)

HR for mPFS

mOS (months)

HR for mOS

 ≥ G3 AE (%)

Refs.

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]

  1. CT, chemotherapy; G3 AE, grade 3 adverse event; HR, hazard ratio; ICI, immune checkpoint inhibitor; mOS, median overall survival; mPFS, median progression-free survival; NSCLC, non-small cell lung cancer; ORR, objective response rate; TKI, tyrosine kinase inhibitor.
  2. *Combined with data from KN046-CHN-001.
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Journal of Hematology & Oncology

ISSN: 1756-8722

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