Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations
AVANZAR
A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR)
2 other identifiers
interventional
1,350
23 countries
254
Brief Summary
This is a Phase III, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2022
Longer than P75 for phase_3
254 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 28, 2022
CompletedStudy Start
First participant enrolled
December 29, 2022
CompletedFirst Posted
Study publicly available on registry
January 18, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2027
April 22, 2026
April 1, 2026
4.8 years
December 28, 2022
April 21, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Progression-Free Survival (PFS) by blinded independent central review (BICR) in the non-squamous TROP2 biomarker positive population
PFS is defined as time from randomisation until progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by BICR, or death due to any cause.
Approximately 3 years
Overall Survival (OS) in the non-squamous TROP2 biomarker positive population
OS is defined as the time from randomisation until the date of death due to any cause.
Approximately 5 years
PFS by BICR in the non-squamous population
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
Approximately 3 years
OS in the non-squamous population
OS is defined as the time from randomisation until the date of death due to any cause.
Approximately 5 years
Secondary Outcomes (9)
PFS by BICR in ITT and TROP2 biomarker-defined populations
Approximately 3 years
OS in ITT and TROP2 biomarker-defined populations
Approximately 5 years
Objective Response Rate (ORR) in ITT, non-squamous and TROP2 biomarker-defined populations
Approximately 5 years
Duration of Response (DoR) in ITT, non-squamous and TROP2 biomarker-defined populations
Approximately 5 years
PFS by investigator in ITT, non-squamous and TROP2 biomarker-defined populations
Approximately 3 years
- +4 more secondary outcomes
Other Outcomes (1)
Safety of Dato-DXd in combination with durvalumab and carboplatin
Approximately 5 years
Study Arms (2)
Dato-DXd + Durvalumab + Carboplatin
EXPERIMENTALParticipants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve \[AUC\] 5 mg/mL/minute.
Histologic-specific therapy
ACTIVE COMPARATORNon-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin. Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin.
Interventions
Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle for a maximum of 35 cycles or 2 years (whichever occurs first).
Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
Eligibility Criteria
You may qualify if:
- Participants ≥ 18 years at screening
- Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
- Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations).
- Testing is not required for tumors with squamous histology, with exceptions.
- ECOG PS of 0 or 1
- Archival tumour tissue
- Has adequate bone marrow reserve and organ function within 7 days before randomization
You may not qualify if:
- Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
- History of another primary malignancy with exceptions
- Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
- Spinal cord compression or clinically or radiologically active brain metastases
- History of leptomeningeal carcinomatosis.
- Known active or uncontrolled hepatitis B or C virus infection.
- Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
- Clinically significant corneal disease
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (254)
Research Site
Phoenix, Arizona, 85054, United States
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Tucson, Arizona, 85704, United States
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Hot Springs, Arkansas, 71913, United States
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Little Rock, Arkansas, 72205, United States
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Springdale, Arkansas, 72762, United States
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Fountain Valley, California, 92708, United States
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Los Angeles, California, 90017, United States
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Orange, California, 92868, United States
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Boulder, Colorado, 80303, United States
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Fort Myers, Florida, 33901, United States
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Jacksonville, Florida, 32224, United States
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St. Petersburg, Florida, 33705, United States
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West Palm Beach, Florida, 33401, United States
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Hinsdale, Illinois, 60521, United States
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Fort Wayne, Indiana, 46845, United States
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Bettendorf, Iowa, 52722, United States
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Iowa City, Iowa, 52242, United States
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Waukee, Iowa, 50263, United States
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Baton Rouge, Louisiana, 70808, United States
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Covington, Louisiana, 70433, United States
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Duluth, Minnesota, 55805, United States
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Rochester, Minnesota, 55905, United States
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Hannibal, Missouri, 63401, United States
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Lincoln, Nebraska, 68506, United States
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Lincoln, Nebraska, 68516, United States
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Clifton Park, New York, 12065, United States
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Asheville, North Carolina, 28806, United States
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Canton, Ohio, 44710, United States
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Columbus, Ohio, 43219, United States
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Maumee, Ohio, 43537, United States
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Tulsa, Oklahoma, 74134, United States
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Portland, Oregon, 97239, United States
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Salem, Oregon, 97301, United States
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Philadelphia, Pennsylvania, 19104, United States
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Philadelphia, Pennsylvania, 19107, United States
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Philadelphia, Pennsylvania, 19111, United States
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York, Pennsylvania, 17403, United States
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Watertown, South Dakota, 57201, United States
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Memphis, Tennessee, 38120, United States
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Dallas, Texas, 75246, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77030, United States
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Houston, Texas, 77090, United States
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Irving, Texas, 75063, United States
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Fairfax, Virginia, 22031, United States
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Henrico, Virginia, 23229, United States
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Norfolk, Virginia, 23502, United States
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Renton, Washington, 98055, United States
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Spokane, Washington, 99202, United States
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Tacoma, Washington, 98405, United States
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Appleton, Wisconsin, 54911, United States
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La Crosse, Wisconsin, 54601, United States
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Graz, 8036, Austria
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Rankweil, 6830, Austria
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Vienna, 1090, Austria
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Vienna, 1210, Austria
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Blumenau, 89010-340, Brazil
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Florianópolis, 88034-000, Brazil
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Fortaleza, 60336-045, Brazil
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Londrina, 86015-520, Brazil
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Porto Alegre, 90035-903, Brazil
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São Paulo, 01246-000, Brazil
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São Paulo, 01327-001, Brazil
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São Paulo, 01509-900, Brazil
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São Paulo, 09323-900, Brazil
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Taubaté, 12030-200, Brazil
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Vitória, 29043-260, Brazil
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Sofia, 1113, Bulgaria
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Sofia, 1330, Bulgaria
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Varna, 9010, Bulgaria
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Saint John, New Brunswick, E2L 4L2, Canada
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Brampton, Ontario, L6R 3J7, Canada
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Greater Sudbury, Ontario, P3E 5J1, Canada
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Kitchener, Ontario, N2G 1G3, Canada
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Newmarket, Ontario, L3Y 2P9, Canada
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Montreal, Quebec, H1T 2M4, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Montreal, Quebec, H4J 1C5, Canada
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Saint-Jérôme, Quebec, J7Z 5T3, Canada
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Saskatoon, Saskatchewan, S7N 4H4, Canada
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Beijing, 100010, China
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Beijing, 100029, China
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Beijing, 100037, China
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Beijing, 100039, China
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Beijing, 100853, China
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Beijing, CN-100730, China
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Changsha, 410008, China
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Changsha, 410013, China
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Chengdu, 610041, China
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Chengdu, 610072, China
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Chongqing, 400037, China
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Guangzhou, 510000, China
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Guangzhou, 510100, China
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Hefei, 230601, China
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Jinan, 250021, China
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Kunming, 650101, China
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Lanzhou, 730000, China
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Liuchow, 545006, China
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Shandong, China
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Shanghai, 200030, China
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Shanghai, 200032, China
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Shanghai, 200080, China
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Shantou, 515041, China
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Shenyang, 110004, China
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Shenzhen, 517108, China
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Taiyuan, 030000, China
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Tianjin, 300060, China
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Wenzhou, 325000, China
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Wuhan, 430030, China
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Wuhan, 430060, China
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Xiamen, 361004, China
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Yangzhou, 225001, China
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Zhengzhou, 450052, China
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Brest, 29200, France
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Créteil, 94010, France
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Gleizé, 69400, France
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Montpellier, 34070, France
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Nîmes, 30029, France
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Paris, 75018, France
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Paris, 75674, France
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Rouen, 76031, France
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Saint-Quentin, 02321, France
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Strasbourg, 67091, France
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Toulon, 83800, France
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Toulouse, 31059, France
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Tours, 37000, France
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Bad Berka, 99437, Germany
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Berlin, 14109, Germany
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Frankfurt A. Main, 60590, Germany
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Gauting, 82131, Germany
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Gütersloh, 33332, Germany
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Hamburg, 20251, Germany
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Kassel, 34125, Germany
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Kiel, 24116, Germany
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Koblenz, 56073, Germany
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Minden, 32429, Germany
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Rosenheim, 83022, Germany
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Velbert, 42551, Germany
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Würzburg, 97074, Germany
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Athens, 11526, Greece
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Athens, 11527, Greece
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Athens, 155 62, Greece
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Piraeus, 185 47, Greece
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Thessaloniki, 55236, Greece
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Thessaloniki, 57001, Greece
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Budapest, 1121, Hungary
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Budapest, 1122, Hungary
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Gyöngyös - Mátraháza, 3200, Hungary
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Kaposvár, 7400, Hungary
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Pécs, 7624, Hungary
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Szekszárd, 7100, Hungary
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Szolnok, 5000, Hungary
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Törökbálint, 2045, Hungary
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Calicut, 673601, India
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Delhi, 110029, India
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Delhi, 110085, India
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Jaipur, 302017, India
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Kolkata, 700160, India
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Madurai, 625107, India
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Puducherry, 605006, India
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Florence, 50134, Italy
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Lecco, 23900, Italy
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Messina, 98158, Italy
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Naples, 80131, Italy
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Orbassano, 10043, Italy
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Padova, 35128, Italy
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Parma, 43126, Italy
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Peschiera del Garda, 37019, Italy
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Rozzano, 20089, Italy
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Bunkyō City, 113-8603, Japan
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Chūōku, 104-0045, Japan
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Hamamatsu, 431-3192, Japan
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Hamamatsu, 432-8580, Japan
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Hidaka-shi, 350-1298, Japan
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Hirosaki-shi, 036-8563, Japan
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Hiroshima, 730-8518, Japan
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Kumamoto, 860-8556, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 466-8560, Japan
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Okayama, 700-8558, Japan
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Osaka, 545-8586, Japan
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Osakasayama-shi, 589-8511, Japan
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Sapporo, 060-8638, Japan
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Sunto-gun, 411-8777, Japan
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Wakayama, 641-8510, Japan
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Yokohama, 221-0855, Japan
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Yokohama, 241-8515, Japan
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Del. Cuauhtemoc, 06700, Mexico
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Mexico City, 03810, Mexico
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México, 14080, Mexico
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San Luis Potosí City, 78209, Mexico
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Arequipa, 04002, Peru
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Concepción, 12125, Peru
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Lima, 15036, Peru
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Lima, 34, Peru
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Lima, LIMA 27, Peru
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Lima, LIMA 29, Peru
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Bydgoszcz, 85-796, Poland
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Bystra, 43-360, Poland
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Grudziądz, 86-300, Poland
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Kielce, 25-734, Poland
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Koszalin, 75-581, Poland
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Olsztyn, 10-357, Poland
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Poznan, 60-569, Poland
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Przemyśl, 37-700, Poland
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Racibórz, 47-400, Poland
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Radom, 26-600, Poland
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Siedlce, 08-110, Poland
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Busan, 48108, South Korea
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Cheongju-si, 28644, South Korea
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Jinju, 52727, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Seoul, 07061, South Korea
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Suwon, 16247, South Korea
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Suwon, 16499, South Korea
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Las Palmas de Gran Canaria, 35016, Spain
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Lugo, 27003, Spain
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Madrid, 28041, Spain
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Santander, 39008, Spain
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Seville, 41013, Spain
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Valencia, 46010, Spain
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Zaragoza, 50009, Spain
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Gävle, 801 88, Sweden
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Linköping, 581 85, Sweden
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Lund, 221 85, Sweden
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Stockholm, 17176, Sweden
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Uppsala, 751 85, Sweden
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Hsinchu, 300, Taiwan
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New Taipei City, 235, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 73657, Taiwan
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Taipei, 11217, Taiwan
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Taoyuan District, 333, Taiwan
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Adana, 01060, Turkey (Türkiye)
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Ankara, 06800, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Istanbul, 34098, Turkey (Türkiye)
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Izmir, 35110, Turkey (Türkiye)
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Aberdeen, AB25 2ZN, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Cardiff, CF14 2TL, United Kingdom
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Cheltenham, GL53 7AN, United Kingdom
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Edinburgh, EH4 2XU, United Kingdom
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London, SE1 9RT, United Kingdom
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London, W6 8RF, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Middlesbrough, TS4 3BW, United Kingdom
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Newcastle upon Tyne, NE7 7DN, United Kingdom
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Taunton, TA1 5DA, United Kingdom
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Hanoi, 100000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Charu Aggarwal
Perelman Center for Advanced Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- None (Open Label)
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 28, 2022
First Posted
January 18, 2023
Study Start
December 29, 2022
Primary Completion (Estimated)
November 1, 2027
Study Completion (Estimated)
November 1, 2027
Last Updated
April 22, 2026
Record last verified: 2026-04
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/PhRMA Data-Sharing Principles. For details of our timelines, please refer 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 anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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.