Non-small Cell Lung Cancer
Conditions
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
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.
Interventions
DRUGDatopotamab Deruxtecan
Datopotamab Deruxtecan IV (intravenous)
DRUGRilvegostomig
Rilvegostomig IV (intravenous)
DRUGCarboplatin
Carboplatin IV (intravenous), Active Comparator
DRUGCisplatin
Cisplatin IV (intravenous), Active Comparator
DRUGEtoposide
Etoposide IV (intravenous), Active Comparator
DRUGPemetrexed
Pemetrexed IV (intravenous), Active Comparator
DRUGVinorelbine
Vinorelbine IV (intravenous), Active Comparator
DRUGUFT
UFT Oral route of administration, Active Comparator
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Open-label, sponsor-blinded
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)).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From date of randomisation up to approximately 10 years. | The analysis will include all randomised participants as randomised. All events will be included, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy. The measure of interest is the HR of DFS. Descriptive analyses of Dato-DXd in combination with rilvegostomig versus rilvegostomig monotherapy and rilvegostomig monotherapy versus SoC will be performed to assess contribution of components. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From date of randomisation up to approximately 10 years. | The analysis will include all randomised participants as randomised. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy. The measure of interest is the HR of OS. Descriptive analyses of Dato-DXd in combination with rilvegostomig versus rilvegostomig monotherapy and rilvegostomig monotherapy versus SoC will be performed to assess contribution of components. |
| 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 | Measured at weeks 12, 24 and 48. | The analysis will include all randomised participants as randomised. The physical function will be measured by the PROMIS SF PF 8c. Data from PROMIS SF PF 8c will capture participants' perceived ability to perform specific activities from daily life and will be scored on a 5-point rating scale. The measure of interest will be the between treatment group difference in adjusted mean in physical function scores. Descriptive analyses of Dato-DXd in combination with rilvegostomig versus rilvegostomig monotherapy and rilvegostomig monotherapy versus SoC will be performed to assess contribution of components. |
| 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 | Measured at weeks 12, 24 and 48. | The analysis will include all randomised participants as randomised. The GHS/QoL scores will be measured by the GHS/QoL scale from EORTC IL172. The measure of interest will be the between treatment group difference in adjusted mean in GHS/QoL scores. Descriptive analyses of Dato-DXd in combination with rilvegostomig versus rilvegostomig monotherapy and rilvegostomig monotherapy versus SoC will be performed to assess contribution of components. |
| Pharmacokinetics (PK) | Up to 30 or 90 days post-last dose of study intervention. | Concentration of Dato-DXd, total anti-TROP2 antibody, and MAAA-1181a (payload deruxtecan) in plasma or serum. |
| Immunogenicity | Up to 30 or 90 days post-last dose of study intervention. | Presence of ADAs for Dato-DXd and rilvegostomig (confirmatory results: titres and neutralising antibodies for confirmed positive samples). |
Countries
Brazil, Canada, Hong Kong, Japan, Malaysia, Taiwan, Thailand, Turkey (Türkiye), United States, Vietnam
Contacts
PRINCIPAL_INVESTIGATORDavid Jones, MD
Memorial Sloan Kettering Cancer Center, New York, United States of America
PRINCIPAL_INVESTIGATOREnriqueta Felip, MD
Vall d'Hebron Hospital, Barcelona, Spain
Outcome results
None listed