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

NCT06564844 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: D926TC000012024-512195-35-00
• Study Type: interventional
• Target: 24
• Locations: 11 countries
• Sites: 99

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 least one high-risk pathological feature.

Conditions

Non-small Cell Lung Cancer

Keywords

Non-small Cell Lung Cancer; NSCLC; Adenocarcinoma; Stage I; Datopotamab Deruxtecan; Dato-DXd; Adjuvant Treatment; Rilvegostomig; Standard of Care; Pemetrexed; Carboplatin; Cisplatin; Vinorelbine; Etoposide; UFT; ctDNA-positive; High-risk Pathological Features

Outcome Measures

Primary Outcomes (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

  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 Outcomes (7)

• 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.

• 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.

• 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.

• Pharmacokinetics (PK)

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

• Pharmacokinetics (PK)

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

Study Arms (3)

Dato-DXd + rilvegostomig

EXPERIMENTAL

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; Drug: Rilvegostomig

Rilvegostomig

EXPERIMENTAL

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

Drug: Rilvegostomig

Standard of Care (SoC)

ACTIVE COMPARATOR

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

Drug: Carboplatin; Drug: Cisplatin; Drug: Etoposide; Drug: Pemetrexed; Drug: Vinorelbine; Drug: UFT

Interventions

Carboplatin DRUG

Carboplatin IV (intravenous), Active Comparator

Standard of Care (SoC)

Datopotamab Deruxtecan DRUG

Datopotamab Deruxtecan IV (intravenous)

Also known as: Dato-DXd, DS-1062a

Dato-DXd + rilvegostomig

Rilvegostomig DRUG

Rilvegostomig IV (intravenous)

Also known as: AZD2936

Dato-DXd + rilvegostomig; Rilvegostomig

Cisplatin DRUG

Cisplatin IV (intravenous), Active Comparator

Standard of Care (SoC)

Etoposide DRUG

Etoposide IV (intravenous), Active Comparator

Standard of Care (SoC)

Pemetrexed DRUG

Pemetrexed IV (intravenous), Active Comparator

Standard of Care (SoC)

Vinorelbine DRUG

Vinorelbine IV (intravenous), Active Comparator

Standard of Care (SoC)

UFT DRUG

UFT Oral route of administration, Active Comparator

Standard of Care (SoC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented treatment-naive Stage I (T \< 4 cm, AJCC 8th ed) adenocarcinoma NSCLC
• Complete surgical resection (R0) of the primary NSCLC
• Unequivocal no evidence of disease at post-surgical
• 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)
• ECOG of 0 or 1, life expectancy of \> 6 months and complete recovery after surgery
• Adequate bone marrow reserve and organ function

You may not qualify if:

• Sensitizing EGFR mutation and/or ALK alteration
• 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
• Significant pulmonary function compromise
• History of another primary malignancy within 3 years (with exceptions)
• Any evidence of severe or uncontrolled systemic diseases, including but not limited to bleeding diseases, active infection and cardiac disease
• Active or prior documented autoimmune or inflammatory disorders (with exceptions)
• Active infection with tuberculosis, hepatitis B or C virus, hepatitis A, or known HIV infection that is not well controlled
• History of active primary immunodeficiency
• Clinically significant corneal disease

Sponsors & Collaborators

• AstraZeneca: lead
• Daiichi Sankyo: collaborator

Study Sites (99)

Research Site

Tucson, Arizona, 85724, United States

Location

Research Site

Duarte, California, 91010, United States

Location

Research Site

Glendale, California, 91204, United States

Location

Research Site

Los Angeles, California, 90089, United States

Location

Research Site

Lone Tree, Colorado, 80124, United States

Location

Research Site

Washington D.C., District of Columbia, 20007, United States

Location

Research Site

Jacksonville, Florida, 32224, United States

Location

Research Site

St. Petersburg, Florida, 33709, United States

Location

Research Site

Chicago, Illinois, 60637, United States

Location

Research Site

Evanston, Illinois, 60201, United States

Location

Research Site

Zion, Illinois, 60099, United States

Location

Research Site

Kansas City, Kansas, 66160, United States

Location

Research Site

Lexington, Kentucky, 40503, United States

Location

Research Site

Baltimore, Maryland, 21237, United States

Location

Research Site

Farmington Hills, Michigan, 48334, United States

Location

Research Site

Grand Rapids, Michigan, 49503, United States

Location

Research Site

Minneapolis, Minnesota, 55407, United States

Location

Research Site

Billings, Montana, 59102, United States

Location

Research Site

Omaha, Nebraska, 68130, United States

Location

Research Site

East Syracuse, New York, 13057, United States

Location

Research Site

Mineola, New York, 11501, United States

Location

Research Site

New York, New York, 10016, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Bethlehem, Pennsylvania, 18015, United States

Location

Research Site

Philadelphia, Pennsylvania, 19107, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15212, United States

Location

Research Site

Knoxville, Tennessee, 37920, United States

Location

Research Site

Memphis, Tennessee, 38120, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Austin, Texas, 78745, United States

Location

Research Site

Dallas, Texas, 75231, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

San Antonio, Texas, 78217, United States

Location

Research Site

Fairfax, Virginia, 22031, United States

Location

Research Site

Edmonds, Washington, 98026, United States

Location

Research Site

Seattle, Washington, 98104, United States

Location

Research Site

Madison, Wisconsin, 53792, United States

Location

Research Site

Barretos, 14784-057, Brazil

Location

Research Site

Brasília, 70200-730, Brazil

Location

Research Site

Florianópolis, 88034-000, Brazil

Location

Research Site

São Paulo, 01323-903, Brazil

Location

Research Site

Teresina, 64049-200, Brazil

Location

Research Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Research Site

Oshawa, Ontario, L1G 2B9, Canada

Location

Research Site

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Research Site

Montreal, Quebec, H2X 3J4, Canada

Location

Research Site

Saskatoon, Saskatchewan, S7M 0Z9, Canada

Location

Research Site

Hong Kong, 999077, Hong Kong

Location

Research Site

Bunkyō City, 113-8603, Japan

Location

Research Site

Chiba, 260-0877, Japan

Location

Research Site

Chūōku, 104-0045, Japan

Location

Research Site

Fukuoka, 812-8582, Japan

Location

Research Site

Hidaka-shi, 350-1298, Japan

Location

Research Site

Hiroshima, 730-8518, Japan

Location

Research Site

Hiroshima, 734-8551, Japan

Location

Research Site

Iwakuni-shi, 740-8510, Japan

Location

Research Site

Kashiwa, 277-8577, Japan

Location

Research Site

Kitaadachi-gun, 362-0806, Japan

Location

Research Site

Kobe, 650-0017, Japan

Location

Research Site

Kōtoku, 135-8550, Japan

Location

Research Site

Kumamoto, 860-8556, Japan

Location

Research Site

Nagoya, 464-8681, Japan

Location

Research Site

Niigata, 951-8566, Japan

Location

Research Site

Osakasayama-shi, 589-8511, Japan

Location

Research Site

Sapporo, 003-0804, Japan

Location

Research Site

Sendai, 980-0873, Japan

Location

Research Site

Sendai, 980-8574, Japan

Location

Research Site

Wakayama, 641-8510, Japan

Location

Research Site

Yokohama, 241-8515, Japan

Location

Research Site

Kuala Lumpur, 50586, Malaysia

Location

Research Site

Kuala Lumpur, 59100, Malaysia

Location

Research Site

Kuching, 93586, Malaysia

Location

Research Site

Kaohsiung City, 80756, Taiwan

Location

Research Site

Taipei, 10002, Taiwan

Location

Research Site

Taipei, 112, Taiwan

Location

Research Site

Taipei, 114, Taiwan

Location

Research Site

Taoyuan District, 333, Taiwan

Location

Research Site

Bangkok, 10400, Thailand

Location

Research Site

Bangkoknoi, 10700, Thailand

Location

Research Site

Banphaeo, 74120, Thailand

Location

Research Site

Dusit, 10300, Thailand

Location

Research Site

Hat Yai, 90110, Thailand

Location

Research Site

Muang, 40002, Thailand

Location

Research Site

Muang, 50200, Thailand

Location

Research Site

Ratchathewi, 10400, Thailand

Location

Research Site

Ankara, 06010, Turkey (Türkiye)

Location

Research Site

Ankara, 06280, Turkey (Türkiye)

Location

Research Site

Istanbul, 34214, Turkey (Türkiye)

Location

Research Site

Mersin, 33240, Turkey (Türkiye)

Location

Research Site

Leeds, LS9 7TF, United Kingdom

Location

Research Site

London, SE1 9RT, United Kingdom

Location

Research Site

Nottingham, NG5 1PB, United Kingdom

Location

Research Site

Da Nang, 550000, Vietnam

Location

Research Site

Hanoi, 100000, Vietnam

Location

Research Site

Hà Nội, 100000, Vietnam

Location

Research Site

Ho Chi Minh City, 700000, Vietnam

Location

Research Site

Ho Chi Minh City, 70000, Vietnam

Location

Research Site

Vinh, 460000, Vietnam

Location

Related Publications (1)

• 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.

  PMID: 40976544 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Adenocarcinoma

Interventions

Carboplatin; Cisplatin; Etoposide; Pemetrexed; Vinorelbine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Open-label, sponsor-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomised in a 2:1:2 ratio to one of the following groups: Arm 1 - Dato-DXd in combination with rilvegostomig, Arm 2 - rilvegostomig monotherapy or Arm 3 - SoC (either observation only or investigator's choice of chemotherapy (ICC)).

Study Record Dates

• First Submitted: August 7, 2024
• First Posted: August 21, 2024
• Study Start: October 15, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (38); TH (8); HK (1); TU (4); TW (5); JP (21); VN (6); BR (5); CA (5); GB (3); MY (3)