Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer
NCT ID: NCT04612751
Last Updated: 2025-12-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1
155 participants
INTERVENTIONAL
2021-02-02
2026-04-30
Brief Summary
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Detailed Description
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Two dose levels of Dato-DXd will be studied in combination with immunotherapy (durvalumab, AZD2936, MEDI5752, or AZD7789) with or without 4 cycles of carboplatin in 15 study cohorts
Each cohort will start with Part 1 (dose escalation or confirmation), where 3 to 9 participants will be assessed for dose-limiting toxicities (DLT) in the first cycle of treatment. if the DLT incidence rate meets the criteria based on the modified toxicity probability interval-2 (mTPI-2), then Part 2 (dose expansion) may be opened.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort 1
Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Cohort 2
Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Cohort 3
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
Cohort 4
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
Cohort 5
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
AZD2936
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 6
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
AZD2936
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 7
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
AZD2936
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 8
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
AZD2936
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 9
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
MEDI5752
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 10
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
MEDI5752
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 11
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
MEDI5752
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 12
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
AZD7789
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 13
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
AZD7789
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 14
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
AZD7789
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Cohort 4A
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC
Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
Interventions
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Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
AZD2936
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
MEDI5752
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
AZD7789
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Daiichi Sankyo
INDUSTRY
AstraZeneca
INDUSTRY
Responsible Party
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Locations
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Research Site
La Jolla, California, United States
Research Site
Santa Ana, California, United States
Research Site
St Louis, Missouri, United States
Research Site
Hackensack, New Jersey, United States
Research Site
Cleveland, Ohio, United States
Research Site
Philadelphia, Pennsylvania, United States
Research Site
Dallas, Texas, United States
Research Site
Houston, Texas, United States
Research Site
San Antonio, Texas, United States
Research Site
Fairfax, Virginia, United States
Research Site
Hasselt, , Belgium
Research Site
Roeselare, , Belgium
Research Site
Aviano, , Italy
Research Site
Meldola, , Italy
Research Site
Orbassano, , Italy
Research Site
Roma, , Italy
Research Site
Kōtoku, , Japan
Research Site
Sunto-gun, , Japan
Research Site
Yokohama, , Japan
Research Site
Gdansk, , Poland
Research Site
Lodz, , Poland
Research Site
Lublin, , Poland
Research Site
Warsaw, , Poland
Research Site
A Coruña, , Spain
Research Site
Badalona, , Spain
Research Site
Barcelona, , Spain
Research Site
Madrid, , Spain
Research Site
Madrid, , Spain
Research Site
Madrid, , Spain
Research Site
Seville, , Spain
Research Site
Hsinchu, , Taiwan
Research Site
Taichung, , Taiwan
Research Site
Tainan, , Taiwan
Research Site
Taipei, , Taiwan
Research Site
Taipei, , Taiwan
Research Site
Taipei, , Taiwan
Research Site
Taoyuan District, , Taiwan
Research Site
Adana, , Turkey (Türkiye)
Research Site
Ankara, , Turkey (Türkiye)
Research Site
Ankara, , Turkey (Türkiye)
Research Site
Istanbul, , Turkey (Türkiye)
Research Site
Izmir, , Turkey (Türkiye)
Countries
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Related Links
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Lung Cancer Study Locator details (for US)
Other Identifiers
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2021-000274-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-505992-54-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
D926FC00001
Identifier Type: -
Identifier Source: org_study_id