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 3Active Not RecruitingNCT06564844

AstraZeneca24 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Non-small Cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

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.

Time frame: From date of randomisation up to approximately 10 years.

Secondary Outcomes

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

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.

Time frame: From date of randomisation up to approximately 10 years.

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

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.

Time frame: Measured at weeks 12, 24 and 48.

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

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.

Time frame: Measured at weeks 12, 24 and 48.

Pharmacokinetics (PK)

Concentration of Dato-DXd, total anti-TROP2 antibody, and MAAA-1181a (payload deruxtecan) in plasma or serum.

Time frame: Up to 30 or 90 days post-last dose of study intervention.

Pharmacokinetics (PK)

Concentration of rilvegostomig in plasma or serum.

Time frame: Up to 30 or 90 days post-last dose of study intervention.

Pharmacokinetics (PK)

PK parameters (peak and through concentrations).

Time frame: Up to 30 or 90 days post-last dose of study intervention.

Immunogenicity

Presence of ADAs for Dato-DXd and rilvegostomig (confirmatory results: titres and neutralising antibodies for confirmed positive samples).

Time frame: Up to 30 or 90 days post-last dose of study intervention.

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

Overview

Conditions

Interventions

Eligibility

Locations (99)

Outcomes

Primary Outcomes

Secondary Outcomes