Actively Recruiting

Phase 1
Age: 18Years +
All Genders
NCT04686305

Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC

Led by AstraZeneca · Updated on 2026-04-13

304

Participants Needed

91

Research Sites

329 weeks

Total Duration

On this page

Sponsors

A

AstraZeneca

Lead Sponsor

D

Daiichi Sankyo

Collaborating Sponsor

AI-Summary

What this Trial Is About

DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with Immunotherapy Agents with and without chemotherapy in patients with HER2 over-expressing non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.

CONDITIONS

Official Title

Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Histologically documented unresectable locally advanced or metastatic non-squamous NSCLC
  • For Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic disease
  • For Parts 3, 4, and 5: Tumors must not have known genomic alterations or actionable driver kinases with approved therapies
  • For Parts 3, 4, and 5: Treatment-na�ve for advanced or metastatic NSCLC; prior adjuvant, neoadjuvant chemotherapy or definitive chemoradiation allowed if progression occurred more than 6 months after last therapy
  • HER2 overexpression confirmed by central tumor tissue review
  • ECOG performance status of 0 or 1
  • Measurable target disease by RECIST 1.1
  • Adequate organ and bone marrow function as defined by protocol
  • For Parts 3, 4, and 5: Minimum body weight of 35 kg
Not Eligible

You will not qualify if you...

  • Known HER2 mutation
  • History of non-infectious interstitial lung disease or pneumonitis requiring steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis not ruled out by imaging
  • Significant lung diseases including prior pneumonectomy
  • Active primary immunodeficiency, known HIV infection, active or unresolved hepatitis B or hepatitis C infection (with exceptions for negative HCV RNA PCR)
  • Active infection requiring intravenous antibiotics, antivirals, or antifungals
  • Spinal cord compression or active, untreated symptomatic central nervous system metastases
  • Recent myocardial infarction within 6 months, symptomatic congestive heart failure (NYHA Class II-IV), serious cardiac arrhythmias, or recent major cardiovascular events
  • For Parts 3, 4, and 5: Cardiomyopathy, symptomatic CHF (NYHA Class > II), unstable angina, history of MI within 12 months, cardiac arrhythmia, or elevated troponin without symptoms without cardiology clearance
  • Ascites or pericardial effusion requiring drainage or shunts
  • For Parts 3, 4, and 5: Active non-infectious skin disease requiring systemic treatment or autoimmune/inflammatory disorders needing chronic immunosuppression
  • Unresolved toxicities greater than Grade 1 from prior anticancer therapy or prior study therapy discontinuation due to toxicity
  • Contraindications to platinum chemotherapy
  • For Parts 3, 4, and 5: Prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT, or experimental immunotherapy
  • History of substance abuse or medical/psychological conditions interfering with study participation
  • For Parts 3, 4, and 5: History of thromboembolic events within 3 months before first study drug dose (including pulmonary embolism, DVT, or cerebral venous sinus thrombosis)

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 91 locations

1

Research Site

Duarte, California, United States, 91010

Withdrawn

2

Research Site

Newport Beach, California, United States, 92663

Withdrawn

3

Research Site

Orange, California, United States, 92868

Actively Recruiting

4

Research Site

Santa Rosa, California, United States, 95403

Withdrawn

5

Research Site

Westwood, Kansas, United States, 66205

Withdrawn

6

Research Site

Baltimore, Maryland, United States, 21287

Actively Recruiting

7

Research Site

Detroit, Michigan, United States, 48201

Withdrawn

8

Research Site

Buffalo, New York, United States, 14263

Withdrawn

9

Research Site

New York, New York, United States, 10029

Withdrawn

10

Research Site

The Bronx, New York, United States, 10461

Withdrawn

11

Research Site

Houston, Texas, United States, 77030

Actively Recruiting

12

Research Site

Fairfax, Virginia, United States, 22031

Actively Recruiting

13

Research Site

Tacoma, Washington, United States, 98405

Withdrawn

14

Research Site

Adelaide, Australia, 5000

Terminated

15

Research Site

Heidelberg, Australia, 3084

Withdrawn

16

Research Site

Nedlands, Australia, 6009

Actively Recruiting

17

Research Site

Edegem, Belgium, 2650

Completed

18

Research Site

Barretos, Brazil, 14784-400

Actively Recruiting

19

Research Site

Porto Alegre, Brazil, 90035-903

Actively Recruiting

20

Research Site

São Paulo, Brazil, 05652-900

Actively Recruiting

21

Research Site

Winnipeg, Manitoba, Canada, R3E 0V9

Withdrawn

22

Research Site

London, Ontario, Canada, N6A 5W9

Withdrawn

23

Research Site

Montreal, Quebec, Canada, H3T 1E2

Actively Recruiting

24

Research Site

Changchun, China, 130000

Not Yet Recruiting

25

Research Site

Chengdu, China, 610041

Not Yet Recruiting

26

Research Site

Fuzhou, China, 350011

Not Yet Recruiting

27

Research Site

Shandong, China

Not Yet Recruiting

28

Research Site

Shanghai, China, 200433

Actively Recruiting

29

Research Site

Zhengzhou, China, 450000

Not Yet Recruiting

30

Research Site

Bordeaux, France, 33075

Withdrawn

31

Research Site

Dijon, France, 21079

Actively Recruiting

32

Research Site

Pierre-Bénite, France, 69495

Actively Recruiting

33

Research Site

Saint-Herblain, France, 44800

Actively Recruiting

34

Research Site

Villejuif, France, 94805

Actively Recruiting

35

Research Site

Kfar Saba, Israel, 4428164

Actively Recruiting

36

Research Site

Tel Litwinsky, Israel, 52620

Actively Recruiting

37

Research Site

Milan, Italy, 20133

Completed

38

Research Site

Milan, Italy, 20162

Actively Recruiting

39

Research Site

Monza, Italy, 20052

Actively Recruiting

40

Research Site

Naples, Italy, 80131

Actively Recruiting

41

Research Site

Padova, Italy, 35128

Withdrawn

42

Research Site

George Town, Malaysia, 10450

Actively Recruiting

43

Research Site

Kuala Lumpur, Malaysia, 59100

Actively Recruiting

44

Research Site

Kuala Selangor, Malaysia, 62250

Actively Recruiting

45

Research Site

Kuching, Malaysia, 93586

Actively Recruiting

46

Research Site

Amsterdam, Netherlands, 1066 CX

Completed

47

Research Site

Bacolod, Philippines, 6100

Actively Recruiting

48

Research Site

Cebu City, Philippines, 6000

Withdrawn

49

Research Site

City of Taguig, Philippines, 1634

Withdrawn

50

Research Site

Davao City, Philippines, PH-8000

Terminated

51

Research Site

Manila, Philippines, 1000

Terminated

52

Research Site

Manila, Philippines, 1015

Withdrawn

53

Research Site

Quezon City, Philippines, 1100

Actively Recruiting

54

Research Site

Quezon City, Philippines, 1112

Actively Recruiting

55

Research Site

San Juan City, Philippines, 1500

Terminated

56

Research Site

Gdansk, Poland, 80-214

Actively Recruiting

57

Research Site

Krakow, Poland, 30-727

Suspended

58

Research Site

Olsztyn, Poland, 10-357

Actively Recruiting

59

Research Site

Tomaszów Mazowiecki, Poland, 97-200

Terminated

60

Research Site

Warsaw, Poland, 02-781

Actively Recruiting

61

Research Site

Singapore, Singapore, 119228

Completed

62

Research Site

Singapore, Singapore, 168583

Completed

63

Research Site

Singapore, Singapore, 308433

Completed

64

Research Site

Cheongju-si, South Korea, 28644

Actively Recruiting

65

Research Site

Goyang-si, South Korea, 10408

Actively Recruiting

66

Research Site

Jinju, South Korea, 52727

Actively Recruiting

67

Research Site

Seoul, South Korea, 03722

Actively Recruiting

68

Research Site

Seoul, South Korea, 05505

Withdrawn

69

Research Site

Seoul, South Korea, 06351

Actively Recruiting

70

Research Site

Badalona, Spain, 08013

Withdrawn

71

Research Site

Madrid, Spain, 28041

Withdrawn

72

Research Site

Seville, Spain, 41013

Withdrawn

73

Research Site

Valencia, Spain, 46010

Withdrawn

74

Research Site

Kaohsiung City, Taiwan, 833

Actively Recruiting

75

Research Site

Taichung, Taiwan, 402

Actively Recruiting

76

Research Site

Taichung, Taiwan, 40705

Actively Recruiting

77

Research Site

Tainan, Taiwan, 70403

Actively Recruiting

78

Research Site

Taipei, Taiwan, 100

Actively Recruiting

79

Research Site

Taipei, Taiwan, 11217

Actively Recruiting

80

Research Site

Taipei, Taiwan, 235

Actively Recruiting

81

Research Site

Taoyuan, Taiwan, 333

Actively Recruiting

82

Research Site

Bangkok, Thailand, 10300

Actively Recruiting

83

Research Site

Bangkok, Thailand, 10330

Completed

84

Research Site

Hat Yai, Thailand, 90110

Completed

85

Research Site

Khon Kaen, Thailand, 40002

Completed

86

Research Site

Muang, Thailand, 22000

Not Yet Recruiting

87

Research Site

Muang, Thailand, 50200

Actively Recruiting

88

Research Site

Ankara, Turkey (Türkiye), 06800

Actively Recruiting

89

Research Site

Ankara, Turkey (Türkiye), 6200

Actively Recruiting

90

Research Site

Bornova-Izmir, Turkey (Türkiye), 35100

Active, Not Recruiting

91

Research Site

Istanbul, Turkey (Türkiye), 31755

Actively Recruiting

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Research Team

A

AstraZeneca Clinical Study Information Center

CONTACT

A

AstraZeneca Lung Cancer Study Locator Service

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

10

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