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

Phase 3

Recruiting

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Datopotamab Deruxtecan; Drug: Carboplatin; Drug: Rilvegostomig; Drug: Cisplatin; Drug: Etoposide; Drug: Pemetrexed; Drug: Vinorelbine; Drug: UFT

• Registration Number: NCT06564844
• Lead Sponsor: AstraZeneca

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 leas...

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 featur...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Study Timeline

• Study First Submitted: 2024-08-07
• Study First Submitted QC: 2024-08-19
• Study First Posted: 2024-08-21
• Study Start: 2024-10-15
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-16
• Primary Completion: 2031-10-21
• Study Completion: 2035-01-19

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 660

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dato-DXd + rilvegostomig	Datopotamab Deruxtecan	Participants in the Dato-DXd in combination with rilvegostomig group will receive Dato-DXd and rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).
Dato-DXd + rilvegostomig	Rilvegostomig	Participants in the Dato-DXd in combination with rilvegostomig group will receive Dato-DXd and rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).
Rilvegostomig	Rilvegostomig	Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).
Standard of Care (SoC)	Carboplatin	Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
Standard of Care (SoC)	Cisplatin	Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
Standard of Care (SoC)	Pemetrexed	Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
Standard of Care (SoC)	Vinorelbine	Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
Standard of Care (SoC)	Etoposide	Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
Standard of Care (SoC)	UFT	Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).

Primary Outcome Measures

Name	Time	Method
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.; ...

Secondary Outcome Measures

Name	Time	Method
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.; ...
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.; ...
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.; ...
Pharmacokinetics (PK)	Up to 30 or 90 days post-last dose of study intervention.	PK parameters (peak and through concentrations).
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).

Trial Locations

Locations (1)

Research Site; 🇻🇳 Vinh, Vietnam