Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations

NCT05687266
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
1,350
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Lead sponsor
AstraZeneca
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Start date
2022-12-29
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Number of sites
254
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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).
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Acronym
AVANZAR
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Short title
Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations
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Official title
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)
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2027-11-01
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First posted
2023-01-18
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Registry last updated
2026-04-22
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Primary completion date
2027-11-01
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Start date
2022-12-29
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Actual participants
1,350
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Participants
1,350
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Participant count basis
Actual
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Protocol amendments
4
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Randomisation ratio
1:1
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Number of sites
254
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05687266
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ClinicalTrials.gov ID
NCT05687266
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Masking description
None (Open Label)
Sources for study design
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  1. Progression-Free Survival (PFS) by blinded independent central review (BICR) in the non-squamous TROP2 biomarker positive population

    Timeframe: Approximately 3 years

    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.

  2. Overall Survival (OS) in the non-squamous TROP2 biomarker positive population

    Timeframe: Approximately 5 years

    OS is defined as the time from randomisation until the date of death due to any cause.

  3. PFS by BICR in the non-squamous population

    Timeframe: Approximately 3 years

    PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.

  4. OS in the non-squamous population

    Timeframe: Approximately 5 years

    OS is defined as the time from randomisation until the date of death due to any cause.

  1. PFS by BICR in ITT and TROP2 biomarker-defined populations

    Timeframe: Approximately 3 years

    PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.

  2. OS in ITT and TROP2 biomarker-defined populations

    Timeframe: Approximately 5 years

    OS is defined as the time from randomisation until the date of death due to any cause.

  3. Objective Response Rate (ORR) in ITT, non-squamous and TROP2 biomarker-defined populations

    Timeframe: Approximately 5 years

    ORR is defined as the proportion of participants who have a confirmed Complete Response (CR) or confirmed Partial Response (PR), as determined by BICR per RECIST 1.1.

  4. Duration of Response (DoR) in ITT, non-squamous and TROP2 biomarker-defined populations

    Timeframe: Approximately 5 years

    DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR and investigator clinical assessment or death due to any cause.

  5. PFS by investigator in ITT, non-squamous and TROP2 biomarker-defined populations

    Timeframe: Approximately 3 years

    PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by investigator clinical assessment, or death due to any cause.

  6. Pharmacokinetics of Dato-DXd when combined with durvalumab and carboplatin.

    Timeframe: Approximately 5 years

    Concentration of Dato-DXd, total anti-TROP2 antibody, and DXd (payload deruxtecan) in plasma and pharmacokinetic (PK) parameters (such as peak and trough concentrations, as data allow; sparse sampling).

  7. Anti-Drug Antibody (ADA) for Dato-DXd

    Timeframe: Approximately 5 years

    The immunogenicity of Dato-DXd when combined with durvalumab and carboplatin.

  8. Time to Second Progression or Death (PFS2) in ITT, non-squamous and TROP2 biomarker-defined populations

    Timeframe: Approximately 5 years

    PFS2 is defined as the time from randomisation to the earliest of the progression events (following the initial progression), subsequent to first subsequent therapy, or death.

  9. Clinical Outcome Assessments in ITT, non-squamous and TROP2 biomarker-defined populations

    Timeframe: Approximately 5 years

    Clinical Outcome Assessments, such as TTD in pulmonary symptoms (dyspnoea, cough and chest pain) as measured by the NSCLC-SAQ, and TTD in physical functioning as measured by PROMIS Physical Function short form 8c

Sources for outcomes
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Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
130 Years
Healthy volunteers
No

Inclusion:

  • 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

Exclusion:

  • 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.
Sources for eligibility
clinicaltrials.gov

  • Research SitePhoenix, United States
  • Research SiteTucson, United States
  • Research SiteHot Springs, United States
  • Research SiteLittle Rock, United States
  • Research SiteSpringdale, United States
  • Research SiteFountain Valley, United States
  • Research SiteLos Angeles, United States
  • Research SiteOrange, United States
  • Research SiteBoulder, United States
  • Research SiteFort Myers, United States
  • Research SiteJacksonville, United States
  • Research SiteSt. Petersburg, United States
  • Research SiteWest Palm Beach, United States
  • Research SiteHinsdale, United States
  • Research SiteFort Wayne, United States
  • Research SiteBettendorf, United States
  • Research SiteIowa City, United States
  • Research SiteWaukee, United States
  • Research SiteBaton Rouge, United States
  • Research SiteCovington, United States
  • Research SiteDuluth, United States
  • Research SiteRochester, United States
  • Research SiteHannibal, United States
  • Research SiteLincoln, United States
  • Research SiteLincoln, United States

And 229 more, listed on the interactive page.

Sources for sites
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Other registry identifiers

  • 2021-004606-21
Sources for references
clinicaltrials.gov

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