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 (TROPION-Lung12)

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Pemetrexed; Drug: Rilvegostomig; Drug: Datopotamab Deruxtecan; Drug: Cisplatin; Drug: Etoposide; Drug: Carboplatin; Drug: UFT; Drug: Vinorelbine

Study type: Interventional

Funder types: Industry

Identifiers

NCT06564844

D926TC00001

2024-512195-35-00 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 660 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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660 participants in 3 patient groups

Dato-DXd + rilvegostomig

Experimental group

Description:

Participants in the Dato-DXd in combination with rilvegostomig group will receive Dato-DXd and rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).

Treatment:

Drug: Datopotamab Deruxtecan

Drug: Rilvegostomig

Rilvegostomig

Experimental group

Description:

Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).

Treatment:

Drug: Rilvegostomig

Standard of Care (SoC)

Active Comparator group

Description:

Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).

Treatment:

Drug: Vinorelbine

Drug: UFT

Drug: Carboplatin

Drug: Etoposide

Drug: Cisplatin

Drug: Pemetrexed