A trial to learn how well Dato-DXd and rilvegostomig work and how safe they are in participants with stage I adenocarcinoma non-small cell lung cancer (NSCLC) after complete removal through surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-02-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ASTRAZENECA AB

External identifiers

EU CT number

2024-512195-35-00

ClinicalTrials.gov

NCT06564844

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Pharmacoeconomic, Others, Therapy

To demonstrate superiority of adjuvant Dato-DXd in combination with rilvegostomig relative to SoC by assessment of DFS using BICR, following complete tumour resection, in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or have at least one high-risk pathological feature.

Secondary objectives 6

1. To estimate the effectiveness of adjuvant Dato-DXd in combination with rilvegostomig relative to SoC by assessment of OS.
2. To assess participant-reported physical function in participants treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC.
3. To assess participant-reported GHS/QoL in participants treated with adjuvant Dato- DXd in combination with rilvegostomig relative to SoC.
4. To assess the PK of Dato-DXd and rilvegostomig in combination therapy and rilvegostomig monotherapy.
5. To investigate the immunogenicity of Dato-DXd and rilvegostomig in combination therapy and rilvegostomig monotherapy.
6. To assess the safety and tolerability of adjuvant Dato-DXd in combination with rilvegostomig as compared with SoC.

Conditions and MedDRA coding

Stage I adenocarcinoma non-small cell lung cancer (NSCLC) with ctDNA-positive result or high-risk pathological feature

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 baseline scan
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 9

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 A, B or C virus, or known HIV infection that is not well controlled
8. History of active primary immunodeficiency
9. Clinically significant corneal disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 5

1. OS (Overall Survival): 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.
2. Participant-reported physical function: The analysis will include all randomised participants as randomised. The measure of interest will be the between treatment group difference in adjusted mean in physical function scores at Weeks 12, 24 and 48.
3. Participant-reported GHS/QoL: The analysis will include all randomised participants as randomised. The measure of interest will be the between treatment group difference in adjusted mean in GHS/QoL scores at Weeks 12, 24 and 48.
4. Pharmacokinetics (PK): Concentration of rilvegostomig, Dato-DXd, total anti‑TROP2 antibody, and MAAA‑1181a (payload deruxtecan) in serum or plasma and PK parameters (peak and trough concentrations).
5. Immunogenicity: Presence of ADAs for Dato-DXd and rilvegostomig (confirmatory results: titres and neutralizing antibodies for confirmed positive samples).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 5

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

9 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 114 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications