A Phase Ib, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Immunotherapy With or Without Carboplatin in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (Tropion-Lung04)

Study Identifier:
DS1062-A-U104
CT.gov Identifier:
NCT04612751
EudraCT Identifier:
2021-000274-28
EU Trial (CTIS) Number:
2023-505992-54-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

To assess safety, tolerability, and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy with or without carboplatin in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

To also look at how tumors respond to the treatment, and the effect on patients' survival.

To report the first data from Cohorts 1‒4.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Non-Small Cell Lung Cancer
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Cohort 1
    • Read More
  • Drug: Drug: Durvalumab
  • Drug: Experimental: Cohort 2
  • Drug: Experimental: Cohort 3
  • Drug: Drug: Carboplatin
  • Drug: Experimental: Cohort 4
  • Drug: Experimental: Cohort 5
  • Drug: Drug: AZD2936
  • Drug: Experimental: Cohort 6
  • Drug: Experimental: Cohort 7
  • Drug: Experimental: Cohort 8
  • Drug: Experimental: Cohort 9
  • Drug: Drug: MEDI5752
  • Drug: Experimental: Cohort 10
  • Drug: Experimental: Cohort 11
  • Drug: Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
  • Drug: Experimental: Cohort 12
  • Drug: Other Names:
  • Drug: WCLC 2021:
  • Drug: WCLC 2023:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Participant ≥18 years old on the day of signing the ICF (local regulatory requirement to consent should be followed).
    • Histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC, without EGFR or ALK genomic alterations (testing not required for participants with documented squamous histology) and no known genomic alterations in other actionable driver kinases with approved therapies. Participants whose tumors harbor KRAS mutations are eligible for this study.
    • For Cohorts 1 to 4, participants must be treatment-naïve or have received and radiologically progressed after only 1 prior line of systemic chemotherapy, without concomitant immune checkpoint inhibitors for advanced or metastatic NSCLC. For Cohorts 4a, 5 to 11, and 14, participants must be treatment-naïve for advanced or metastatic NSCLC. For Cohorts 12 to 13, participants must be CPI acquired resistant after 1 or 2 prior lines of systemic therapy for advanced or metastatic NSCLC, of which 1 should have contained an approved anti-PD-1/PD L1. Cohort 4a will enroll participants whose tumors have squamous histology only; Cohorts 5 Part 2A and Part 2B as well as Cohorts 12 and 13 will enroll participants whose tumors have non-squamous histology only.
    • Willing and able to undergo a mandatory tumor biopsy. A tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen may be substituted for the biopsy collected during screening. For Cohorts 12 and 13, a tumor sample taken ≤24 months prior to screening is acceptable.
    • Has measurable disease per RECIST1.1 within 28 days prior to Cycle 1 Day 1
    • Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 at screening
    • Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 day 1
    • For Cohorts 5 to 14 only: Documented IHC PD-L1 expression per analytically validated Ventana PD-L1 (SP263) IHC assay, 22C3 PharmDx assay, or 28-8 PharmDx assay
    Exclusion criteria
    • Active or prior documented autoimmune or inflammatory disorders
    • Uncontrolled or significant cardiac disease
    • History of another primary malignancy with exceptions
    • active or uncontrolled hepatitis B or C virus or uncontrolled HIV infection
    • spinal cord compression or clinically active CNS metastases
    • History of (non-infectious) ILD/pneumonitis that required steroids
    • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illness
    • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
    • Clinically significant corneal disease

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Kyriakos Papadopoulos
    Status
    Recruiting
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Ramon Yarza
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer