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
NCT Number: NCT06564844
Acronym: TROPION-Lung12
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Non-small Cell Lung Cancer
Interventions: DRUG: Datopotamab Deruxtecan|DRUG: Rilvegostomig|DRUG: Carboplatin|DRUG: Cisplatin|DRUG: Etoposide|DRUG: Pemetrexed|DRUG: Vinorelbine|DRUG: UFT
Sponsor: AstraZeneca
Collaborators: Daiichi Sankyo
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 660
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-10-28
Completion Date: 2035-02-01
Locations: Research Site, Phoenix, Arizona, 85054, United States|Research Site, Tucson, Arizona, 85710, United States|Research Site, Fountain Valley, California, 92708, United States|Research Site, Los Angeles, California, 90033, United States|Research Site, Los Angeles, California, 90095, United States|Research Site, Orange, California, 92868, United States|Research Site, Santa Barbara, California, 93105, United States|Research Site, Aurora, Colorado, 80045, United States|Research Site, Lone Tree, Colorado, 80124, United States|Research Site, Newark, Delaware, 19713, United States|Research Site, Jacksonville, Florida, 32224, United States|Research Site, Miami Beach, Florida, 33140, United States|Research Site, Miami, Florida, 33136, United States|Research Site, Orlando, Florida, 32803, United States|Research Site, Chicago, Illinois, 60637, United States|Research Site, Dyer, Indiana, 46311, United States|Research Site, Fort Wayne, Indiana, 46804, United States|Research Site, Kansas City, Kansas, 66160, United States|Research Site, Baltimore, Maryland, 21201, United States|Research Site, Boston, Massachusetts, 02114, United States|Research Site, Worcester, Massachusetts, 01655, United States|Research Site, Ann Arbor, Michigan, 48109, United States|Research Site, Detroit, Michigan, 48202, United States|Research Site, Grand Rapids, Michigan, 49503, United States|Research Site, Royal Oak, Michigan, 48073, United States|Research Site, Troy, Michigan, 48098, United States|Research Site, Rochester, Minnesota, 55905, United States|Research Site, Saint Paul, Minnesota, 55102, United States|Research Site, Omaha, Nebraska, 68130, United States|Research Site, Las Vegas, Nevada, 89102, United States|Research Site, Mineola, New York, 11501, United States|Research Site, New York, New York, 10065, United States|Research Site, White Plains, New York, 10601, United States|Research Site, Durham, North Carolina, 27710, United States|Research Site, Cincinnati, Ohio, 45245, United States|Research Site, Cleveland, Ohio, 44195, United States|Research Site, Portland, Oregon, 97213, United States|Research Site, Portland, Oregon, 97239, United States|Research Site, Philadelphia, Pennsylvania, 19107, United States|Research Site, Pittsburgh, Pennsylvania, 15212, United States|Research Site, Pittsburgh, Pennsylvania, 15213, United States|Research Site, Memphis, Tennessee, 38120, United States|Research Site, Nashville, Tennessee, 37203, United States|Research Site, Austin, Texas, 78745, United States|Research Site, Houston, Texas, 77090, United States|Research Site, San Antonio, Texas, 78217, United States|Research Site, Salt Lake City, Utah, 84132, United States|Research Site, Fairfax, Virginia, 22031, United States|Research Site, Norfolk, Virginia, 23502, United States|Research Site, Edegem, 2650, Belgium|Research Site, Hasselt, 3500, Belgium|Research Site, Barretos, 14784-057, Brazil|Research Site, Brasília, 70200-730, Brazil|Research Site, Florianópolis, 88034-000, Brazil|Research Site, Sao Paulo, 01323-903, Brazil|Research Site, Teresina, 64049-200, Brazil|Research Site, St. John's, Newfoundland and Labrador, A1B 3V6, Canada|Research Site, Halifax, Nova Scotia, B3H 2Y9, Canada|Research Site, Newmarket, Ontario, L3Y 2R2, Canada|Research Site, Oshawa, Ontario, L1G 2B9, Canada|Research Site, Greenfield Park, Quebec, J4V 2H1, Canada|Research Site, Montreal, Quebec, H2X 3J4, Canada|Research Site, Angers, 49933, France|Research Site, Marseille, 13915, France|Research Site, Paris Cedex 5, 75248, France|Research Site, Suresnes, 92150, France|Research Site, Toulon, 83000, France|Research Site, Bonn, 53127, Germany|Research Site, Erfurt, 99089, Germany|Research Site, Esslingen, 73730, Germany|Research Site, Gauting, 82131, Germany|Research Site, Gera, 07548, Germany|Research Site, Giessen, 35392, Germany|Research Site, Karlsruhe, 76137, Germany|Research Site, Kempten, 87439, Germany|Research Site, Luebeck, 23538, Germany|Research Site, Würzburg, 97067, Germany|Research Site, Jordan, Hong Kong|Research Site, Budapest, 1033, Hungary|Research Site, Budapest, 1083, Hungary|Research Site, Budapest, 1121, Hungary|Research Site, Budapest, 1122, Hungary|Research Site, Debrecen, 4032, Hungary|Research Site, Pécs, 7624, Hungary|Research Site, Törökbálint, 2045, Hungary|Research Site, Zalaegerszeg, 8000, Hungary|Research Site, Roma, 00168, Italy|Research Site, Chiba-shi, 260-0877, Japan|Research Site, Fukuoka-shi, 812-8582, Japan|Research Site, Hidaka-shi, 350-1298, Japan|Research Site, Hiroshima-shi, 734-8551, Japan|Research Site, Iwakuni-shi, 740-8510, Japan|Research Site, Kashiwa, 277-8577, Japan|Research Site, Kitaadachi-gun, 362-0806, Japan|Research Site, Koto-ku, 135-8550, Japan|Research Site, Kumamoto-shi, 860-8556, Japan|Research Site, Niigata-shi, 951-8566, Japan|Research Site, Osakasayama-shi, 589-8511, Japan|Research Site, Sapporo-shi, 003-0804, Japan|Research Site, Sendai-shi, 980-0873, Japan|Research Site, Sendai-shi, 980-8574, Japan|Research Site, Wakayama-shi, 641-8510, Japan|Research Site, Yokohama-shi, 241-8515, Japan|Research Site, George Town, 10450, Malaysia|Research Site, Kuala Lumpur, 50586, Malaysia|Research Site, Kuala Lumpur, 59100, Malaysia|Research Site, Kuching, 93586, Malaysia|Research Site, Selangor, 62250, Malaysia|Research Site, Rotterdam, 3015 GD, Netherlands|Research Site, Alicante, 03010, Spain|Research Site, Badalona, 08003, Spain|Research Site, Barcelona, 8035, Spain|Research Site, Madrid, 28040, Spain|Research Site, Malaga, 29004, Spain|Research Site, Zaragoza, 50009, Spain|Research Site, Kaohsiung, 80756, Taiwan|Research Site, Taipei, 10002, Taiwan|Research Site, Taipei, 112, Taiwan|Research Site, Taipei, 114, Taiwan|Research Site, Taoyuan, 333, Taiwan|Research Site, Bangkoknoi, 10700, Thailand|Research Site, Banphaeo, 74120, Thailand|Research Site, Dusit, 10300, Thailand|Research Site, Hat Yai, 90110, Thailand|Research Site, Muang, 40002, Thailand|Research Site, Muang, 50200, Thailand|Research Site, Ratchathewi, 10400, Thailand|Research Site, Ankara, 06010, Turkey|Research Site, Ankara, 06280, Turkey|Research Site, Istanbul, 34214, Turkey|Research Site, Mersin, 33240, Turkey|Research Site, Leeds, LS9 7TF, United Kingdom|Research Site, London, SE1 9RT, United Kingdom|Research Site, Nottingham, NG5 1PB, United Kingdom|Research Site, Da Nang, 550000, Vietnam|Research Site, Ha noi, 100000, Vietnam|Research Site, Hanoi, 100000, Vietnam|Research Site, Ho Chi Minh, 700000, Vietnam|Research Site, Vinh, 460000, Vietnam

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.

Primary Outcome Measures: 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: 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.