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)

A Phase III, Randomised, Open-label, Global Study of Adjuvant Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma Non-small Cell Lung Cancer Who Are ctDNA-positive or Have High-risk Pathological Features (TROPION-Lung12)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Datopotamab Deruxtecan; Drug: Rilvegostomig; Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide; Drug: Pemetrexed; Drug: Vinorelbine; Drug: UFT

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Barretos, Brazil, 14784-057
    • Research Site
  • Brasília, Brazil, 70200-730
    • Research Site
  • Florianópolis, Brazil, 88034-000
    • Research Site
  • São Paulo, Brazil, 01323-903
    • Research Site
  • Teresina, Brazil, 64049-200
    • Research Site
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Research Site
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
      • Research Site
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Research Site
• Japan
  • Bunkyō City, Japan, 113-8603
    • Research Site
  • Chiba, Japan, 260-0877
    • Research Site
  • Chūōku, Japan, 104-0045
    • Research Site
  • Fukuoka, Japan, 812-8582
    • Research Site
  • Hidaka-shi, Japan, 350-1298
    • Research Site
  • Hiroshima, Japan, 734-8551
    • Research Site
  • Hiroshima, Japan, 730-8518
    • Research Site
  • Iwakuni-shi, Japan, 740-8510
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Kitaadachi-gun, Japan, 362-0806
    • Research Site
  • Kobe, Japan, 650-0017
    • Research Site
  • Kumamoto, Japan, 860-8556
    • Research Site
  • Kōtoku, Japan, 135-8550
    • Research Site
  • Nagoya, Japan, 464-8681
    • Research Site
  • Niigata, Japan, 951-8566
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Research Site
  • Sapporo, Japan, 003-0804
    • Research Site
  • Sendai, Japan, 980-8574
    • Research Site
  • Sendai, Japan, 980-0873
    • Research Site
  • Wakayama, Japan, 641-8510
    • Research Site
  • Yokohama, Japan, 241-8515
    • Research Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Kuala Lumpur, Malaysia, 50586
    • Research Site
  • Kuching, Malaysia, 93586
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Research Site
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
  • Taipei, Taiwan, 114
    • Research Site
  • Taoyuan, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10400
    • Research Site
  • Bangkoknoi, Thailand, 10700
    • Research Site
  • Banphaeo, Thailand, 74120
    • Research Site
  • Dusit, Thailand, 10300
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
  • Muang, Thailand, 40002
    • Research Site
  • Ratchathewi, Thailand, 10400
    • Research Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06280
    • Research Site
  • Ankara, Turkey (Türkiye), 06010
    • Research Site
  • Mersin, Turkey (Türkiye), 33240
    • Research Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Research Site
  • California
    • Duarte, California, United States, 91010
      • Research Site
    • Glendale, California, United States, 91204
      • Research Site
    • Los Angeles, California, United States, 90089
      • Research Site
  • Colorado
    • Lone Tree, Colorado, United States, 80124
      • Research Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Research Site
    • St. Petersburg, Florida, United States, 33709
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
    • Evanston, Illinois, United States, 60201
      • Research Site
    • Zion, Illinois, United States, 60099
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Research Site
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Research Site
    • Grand Rapids, Michigan, United States, 49503
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Research Site
  • Montana
    • Billings, Montana, United States, 59102
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Research Site
  • New York
    • East Syracuse, New York, United States, 13057
      • Research Site
    • Mineola, New York, United States, 11501
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
    • New York, New York, United States, 10065
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Research Site
    • Memphis, Tennessee, United States, 38120
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Austin, Texas, United States, 78745
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78217
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Ho Chi Minh City, Vietnam, 700000
    • Research Site
  • Hà Nội, Vietnam, 100000
    • Research Site
  • Vinh, Vietnam, 460000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dato-DXd + 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).	Drug: Datopotamab Deruxtecan; Datopotamab Deruxtecan IV (intravenous); Other Names: Dato-DXd, DS-1062a; Drug: Rilvegostomig; Rilvegostomig IV (intravenous); Other Names: AZD2936
Experimental: Rilvegostomig; Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).	Drug: Rilvegostomig; Rilvegostomig IV (intravenous); Other Names: AZD2936
Active Comparator: Standard of Care (SoC); Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).	Drug: Carboplatin; Carboplatin IV (intravenous), Active Comparator; Drug: Cisplatin; Cisplatin IV (intravenous), Active Comparator; Drug: Etoposide; Etoposide IV (intravenous), Active Comparator; Drug: Pemetrexed; Pemetrexed IV (intravenous), Active Comparator; Drug: Vinorelbine; Vinorelbine IV (intravenous), Active Comparator; Drug: UFT; UFT Oral route of administration, Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From date of randomisation up to approximately 10 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Up to 30 or 90 days post-last dose of study intervention.
Pharmacokinetics (PK)	Concentration of rilvegostomig in plasma or serum.	Up to 30 or 90 days post-last dose of study intervention.
Pharmacokinetics (PK)	PK parameters (peak and through concentrations).	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).	Up to 30 or 90 days post-last dose of study intervention.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo
• Investigators: Principal Investigator: David Jones, MD, Memorial Sloan Kettering Cancer Center, New York, United States of America; Principal Investigator: Enriqueta Felip, MD, Vall d'Hebron Hospital, Barcelona, Spain

Publications and helpful links

General Publications

• Jones DR, Opitz I, Harpole D, Yanagawa J, Lim E, Tsutani Y, Tan DSW, Dacic S, Ganti AK, Bodla S, Batig A, Lyfar P, Forcina A, Felip E. TROPION-Lung12: A phase 3 study of adjuvant datopotamab deruxtecan and rilvegostomig in ctDNA-positive or high-risk pathology stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2026 Jan;171(1):1-9. doi: 10.1016/j.jtcvs.2025.09.017. Epub 2025 Sep 19.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Cisplatin; Adenocarcinoma; Carboplatin; Etoposide; Pemetrexed; Vinorelbine; Standard of Care; Non-small Cell Lung Cancer; Datopotamab Deruxtecan; Dato-DXd; Stage I; UFT; Adjuvant Treatment; Rilvegostomig; ctDNA-positive; High-risk Pathological Features
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Alkaloids; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Indoles; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Platinum Compounds; Vinorelbine; Pemetrexed; Etoposide; Carboplatin; Cisplatin
• Other Study ID Numbers: D926TC00001; 2024-512195-35-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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.

All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles.

For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved, AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool.

Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No