Clinical trial NCT06564844: A Phase III, Randomised Study of Adjuvant Dato-DXd in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma NSCLC Who Are ctDNA-positive or Have High-risk Pathological Features
Official title: A Phase III, Randomised, Open-label, Global Study of Adjuvant Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma Non-small Cell Lung Cancer Who Are ctDNA-positive or Have High-risk Pathological Features (TROPION-Lung12)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: Non-small Cell Lung Cancer
NSCLC
Adenocarcinoma
Stage I
Datopotamab Deruxtecan
Dato-DXd
Adjuvant Treatment
Rilvegostomig
Standard of Care
Pemetrexed
Carboplatin
Cisplatin
Vinorelbine
Etoposide
UFT
ctDNA-positive
High-risk Pathological Features
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2024-08-21
Enrollment: 660
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomised in a 2:1:2 ratio to one of the following groups: Arm 1 - Dato-DXd in combination with rilvegostomig, Arm 2 - rilvegostomig monotherapy or Arm 3 - SoC (either observation only or investigator's choice of chemotherapy (ICC)).
Primary purpose: TREATMENT

Brief summary: This is a Phase III, randomised, open-label, multicentre, global study assessing the efficacy and safety of adjuvant Dato-DXd in combination with rilvegostomig compared with SoC, after complete surgical resection (R0) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay, or have at least one high-risk pathological feature.

Detailed description: The primary objective of the study is to assess the efficacy and safety of adjuvant Dato-DXd in combination with rilvegostomig relative to SoC, after complete surgical resection (R0) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay, or have at least one high-risk pathological feature.

Eligibility criteria: Inclusion Criteria:

1. Histologically documented treatment-naive Stage I (T \< 4 cm, AJCC 8th ed) adenocarcinoma NSCLC
2. Complete surgical resection (R0) of the primary NSCLC
3. Unequivocal no evidence of disease at post-surgical
4. Pre-surgical ctDNA-positive result (Stage IA or IB) OR presence of at least one high-risk pathological feature (visceral pleural invasion (VPI), lymphovascular invasion (LVI), high-grade histology) (Stage IB only)
5. ECOG of 0 or 1, life expectancy of \> 6 months and complete recovery after surgery
6. Adequate bone marrow reserve and organ function

Exclusion Criteria:

1. Sensitizing EGFR mutation and/or ALK alteration
2. History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
3. Significant pulmonary function compromise
4. History of another primary malignancy within 3 years (with exceptions)
5. Any evidence of severe or uncontrolled systemic diseases, including but not limited to bleeding diseases, active infection and cardiac disease
6. Active or prior documented autoimmune or inflammatory disorders (with exceptions)
7. Active infection with tuberculosis, hepatitis B or C virus, hepatitis A, or known HIV infection that is not well controlled
8. History of active primary immunodeficiency
9. Clinically significant corneal disease

Primary outcomes:
measure: Disease-Free Survival (DFS) using BICR in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC
timeFrame: From date of randomisation up to approximately 10 years.
Secondary outcomes:
measure: Overall Survival (OS) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC
timeFrame: From date of randomisation up to approximately 10 years.
measure: Participant-reported physical function in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC
timeFrame: Measured at weeks 12, 24 and 48.
measure: Participant-reported GHS/QoL in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC
timeFrame: Measured at weeks 12, 24 and 48.
measure: Pharmacokinetics (PK)
timeFrame: Up to 30 or 90 days post-last dose of study intervention.
measure: Pharmacokinetics (PK)
timeFrame: Up to 30 or 90 days post-last dose of study intervention.
measure: Pharmacokinetics (PK)
timeFrame: Up to 30 or 90 days post-last dose of study intervention.
measure: Immunogenicity
timeFrame: Up to 30 or 90 days post-last dose of study intervention.
Other outcomes:
Locations:
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country: Malaysia
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country: Malaysia
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country: Malaysia
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country: Malaysia
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city: Rotterdam
country: Netherlands
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country: Poland
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country: Poland
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country: Poland
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city: Alicante
country: Spain
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city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
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city: Madrid
country: Spain
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city: Malaga
country: Spain
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city: Zaragoza
country: Spain
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city: Solna
country: Sweden
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city: Zurich
country: Switzerland
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city: Kaohsiung
country: Taiwan
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city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkoknoi
country: Thailand
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city: Bangkok
country: Thailand
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city: Banphaeo
country: Thailand
facility: Research Site
city: Dusit
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Muang
country: Thailand
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city: Muang
country: Thailand
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city: Ratchathewi
country: Thailand
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city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
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city: Istanbul
country: Turkey
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city: Mersin
country: Turkey
facility: Research Site
city: Leeds
country: United Kingdom
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city: London
country: United Kingdom
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city: Nottingham
country: United Kingdom
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city: Da Nang
country: Vietnam
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country: Vietnam
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city: Hanoi
country: Vietnam
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city: Ho Chi Minh
country: Vietnam
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city: Ho Chi Minh
country: Vietnam
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city: Vinh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center, New York, United States of America
name: David Jones, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vall d'Hebron Hospital, Barcelona, Spain
name: Enriqueta Felip, MD
role: PRINCIPAL_INVESTIGATOR
References: