Advanced or Metastatic NSCLCPhase 1TROPION-Lung04NCT04612751
Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer
A Phase 1 study testing Datopotamab deruxtecan, Durvalumab and Carboplatin in people with Advanced or Metastatic NSCLC, run by AstraZeneca at 42 sites in 8 countries.
Trial summary
This study will 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic NSCLC
- What is being tested?
- Datopotamab deruxtecan, Durvalumab and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 42 sitesin 8 countries
- Study dates
- 2 Feb 2021to 4 May 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illness
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Clinically significant corneal disease
Trial locations and contacts
42 sites in 8 countries.
42 sites in 8 countries
United States10 sites
Research Site
Cleveland, Ohio, 44106
Research Site
Dallas, Texas, 75230
Research Site
Fairfax, Virginia, 22031
Research Site
Hackensack, New Jersey, 07601
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093
Research Site
Philadelphia, Pennsylvania, 19111
Research Site
San Antonio, Texas, 78229
Research Site
Santa Ana, California, 92705
Research Site
St Louis, Missouri, 63110
Spain7 sites
Research Site
A Coruña, 15005
Research Site
Badalona, 08916
Research Site
Barcelona, 8036
Research Site
Madrid, 28034
Research Site
Madrid, 28046
Research Site
Madrid, 28050
Research Site
Seville, 41015
Taiwan7 sites
Research Site
Hsinchu, 300
Research Site
Taichung, 40705
Research Site
Tainan, 704
Research Site
Taipei, 100
Research Site
Taipei, 110
Research Site
Taipei, 11217
Research Site
Taoyuan, 00333
Turkey (Türkiye)5 sites
Research Site
Adana, 01060
Research Site
Ankara, 06800
Research Site
Ankara, 6200
Research Site
Istanbul, 34010
Research Site
Izmir, 35330
Italy4 sites
Research Site
Aviano, 33081
Research Site
Meldola, 47014
Research Site
Orbassano, 10043
Research Site
Roma, 00144
Poland4 sites
Research Site
Gdansk, 80-952
Research Site
Lodz, 93-338
Research Site
Lublin, 20-090
Research Site
Warsaw, 02-781
Japan3 sites
Research Site
Kōtoku, 135-8550
Research Site
Sunto-gun, 411-8777
Research Site
Yokohama, 241-8515
About this study
Official title: A Phase 1b, 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)
This study will 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).
Read the detailed description
The primary objective is to assess the safety and tolerability of Dato-DXd in combination with immunotherapy with or without 4 cycles of carboplatin in participants with advanced or metastatic NSCLC.
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
- Advanced or Metastatic NSCLC
- Being tested
- Datopotamab deruxtecan, Durvalumab, Carboplatin, AZD2936, MEDI5752
- Keywords
- Advanced or Metastatic NSCLC, Datopotamab deruxtecan (Dato-DXd), DS-1062a, Durvalumab, AZD2936, MEDI5752, AZD7789
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Datopotamab deruxtecanDrug
Also called Dato-DXd
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
DurvalumabDrug
Also called Imfinzi
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
CarboplatinDrug
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
AZD2936Drug
Also called rilvegostomig
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
MEDI5752Drug
Also called volrustomig
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
AZD7789Drug
Also called sabestomig
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 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 Receives: Drug: Datopotamab deruxtecan; Drug: Durvalumab |
| Cohort 2 | Experimental | 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 Receives: Drug: Datopotamab deruxtecan; Drug: Durvalumab |
| Cohort 3 | Experimental | 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 Receives: Drug: Datopotamab deruxtecan; Drug: Durvalumab; Drug: Carboplatin |
| Cohort 4 | Experimental | 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 Receives: Drug: Datopotamab deruxtecan; Drug: Durvalumab; Drug: Carboplatin |
| Cohort 5 | Experimental | Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: AZD2936 |
| Cohort 6 | Experimental | Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: AZD2936 |
| Cohort 7 | Experimental | Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: Carboplatin; Drug: AZD2936 |
| Cohort 8 | Experimental | Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: Carboplatin; Drug: AZD2936 |
| Cohort 9 | Experimental | Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: Carboplatin; Drug: MEDI5752 |
| Cohort 10 | Experimental | Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: Carboplatin; Drug: MEDI5752 |
| Cohort 11 | Experimental | Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: MEDI5752 |
| Cohort 12 | Experimental | Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: AZD7789 |
| Cohort 13 | Experimental | Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: AZD7789 |
| Cohort 14 | Experimental | Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: AZD7789 |
| Cohort 4A | Experimental | Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC Receives: Drug: Datopotamab deruxtecan; Drug: Durvalumab; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with DLTs; TEAEs and other safety parameters during the study.
DLTs, TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings
Measured: DLTs: within first cycle (21 days); TEAEs and other safety parameters: when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up (approximately 60 months)
Secondary outcomes (12)
ORR as assessed by investigator per RECIST Version 1.1
ORR is defined as the proportion of participants with measurable disease at baseline who achieved a BOR of confirmed CR or confirmed PR.
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Duration of Response as assessed by investigator per RECIST version 1.1
Duration of Response is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first documentation of objective PD, or death due to any cause, whichever occurs first.
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Disease Control Rate as assessed by the investigator per RECIST version 1.1
Disease Control Rate is defined as the proportion of participants who achieved a Best Overall Response of confirmed complete response, confirmed partial response, or stable disease.
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Progression-free Survival as assessed by the investigator per RECIST v1.1
Progression-free Survival is defined as the time interval from the date of the start of study treatment to the earlier of the dates of the first documentation of objective PD or death due to any cause, whichever occurs first
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Time to Response as assessed by investigator per RECIST Version 1.1
Time to Response is defined as the time from the date of the start of study treatment to the date of the first documentation of objective response (confirmed complete response or confirmed partial response)
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Best percentage change in the Sum of Diameters of measurable tumors
The best percentage change in the Sum of Diameters of measurable tumors is defined as the percentage change in the smallest Sum of Diameters from all postbaseline tumor assessments, taking as reference the baseline Sum of Diameters.
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Overall Survival
Overall Survival is defined as the time from the date of the start of study treatment to the date of death due to any cause
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Pharmacokinetic Parameter Maximum Plasma/Serum Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a. Serum concentrations of durvalumab and MEDI5752, AZD2936, MEDI5752 and AZD7789.
Cmax = Maximum concentration
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Pharmacokinetic Parameter Time to Maximum Plasma/Serum Concentration (Tmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.
Tmax = time to reach maximum concentration.
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.
Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Prevalence of Dato-Dxd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA
ADA prevalence is defined as the proportion of all participants having ADA at any point in time (including pre-existing ADA at baseline and treatment-emergent ADA)
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Incidence of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA
ADA incidence is defined as the proportion of participants having treatment-emergent ADA during the study period
Measured: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2020
- Study start2 Feb 2021
- Primary completion4 May 2026
- Study completion4 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic NSCLCStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Dose escalation and dose expansion model
- Masking
- None (open label)
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04612751
- Sponsor's protocol ID
- D926FC00001
- Other IDs
- 2023-505992-54-00, 2021-000274-28, 2023
- Acronym
- TROPION-Lung04
- Status last verified
- Jul 2026
- First submitted
- 21 Oct 2020
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, 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)
- ClinicalTrials.gov ID
- NCT04612751
- Acronym / sponsor ID
- TROPION-Lung04 / D926FC00001
- Conditions
- Advanced or Metastatic NSCLC
- Keywords
- Advanced or Metastatic NSCLC, Datopotamab deruxtecan (Dato-DXd), DS-1062a, Durvalumab, AZD2936, MEDI5752, AZD7789
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 155 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Study start
- 2 Feb 2021 (actual)
- Primary completion
- 4 May 2026 (actual)
- Study completion
- 4 May 2027 (estimated)
- First posted
- 3 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will 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).
Detailed description
The primary objective is to assess the safety and tolerability of Dato-DXd in combination with immunotherapy with or without 4 cycles of carboplatin in participants with advanced or metastatic NSCLC.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 15
- Model description
- Dose escalation and dose expansion model
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: Datopotamab deruxtecan, Drug: DurvalumabDatopotamab 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 |
| Cohort 2 | Experimental | Drug: Datopotamab deruxtecan, Drug: DurvalumabDatopotamab 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 |
| Cohort 3 | Experimental | Drug: Datopotamab deruxtecan, Drug: Durvalumab, Drug: CarboplatinDatopotamab 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 |
| Cohort 4 | Experimental | Drug: Datopotamab deruxtecan, Drug: Durvalumab, Drug: CarboplatinDatopotamab 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 |
| Cohort 5 | Experimental | Drug: Datopotamab deruxtecan, Drug: AZD2936Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC |
| Cohort 6 | Experimental | Drug: Datopotamab deruxtecan, Drug: AZD2936Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC |
| Cohort 7 | Experimental | Drug: Datopotamab deruxtecan, Drug: Carboplatin, Drug: AZD2936Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC |
| Cohort 8 | Experimental | Drug: Datopotamab deruxtecan, Drug: Carboplatin, Drug: AZD2936Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC |
| Cohort 9 | Experimental | Drug: Datopotamab deruxtecan, Drug: Carboplatin, Drug: MEDI5752Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC |
| Cohort 10 | Experimental | Drug: Datopotamab deruxtecan, Drug: Carboplatin, Drug: MEDI5752Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC |
| Cohort 11 | Experimental | Drug: Datopotamab deruxtecan, Drug: MEDI5752Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC |
| Cohort 12 | Experimental | Drug: Datopotamab deruxtecan, Drug: AZD7789Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC |
| Cohort 13 | Experimental | Drug: Datopotamab deruxtecan, Drug: AZD7789Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC |
| Cohort 14 | Experimental | Drug: Datopotamab deruxtecan, Drug: AZD7789Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC |
| Cohort 4A | Experimental | Drug: Datopotamab deruxtecan, Drug: Durvalumab, Drug: CarboplatinDatopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Datopotamab deruxtecanAlso: Dato-DXdIntravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle | Drug | Cohort 1, Cohort 10, Cohort 11, Cohort 12, Cohort 13, Cohort 14, Cohort 2, Cohort 3, Cohort 4, Cohort 4A, Cohort 5, Cohort 6, Cohort 7, Cohort 8, Cohort 9 |
| DurvalumabAlso: ImfinziIntravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 4A |
| CarboplatinIntravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle | Drug | Cohort 10, Cohort 3, Cohort 4, Cohort 4A, Cohort 7, Cohort 8, Cohort 9 |
| AZD2936Also: rilvegostomigIntravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle | Drug | Cohort 5, Cohort 6, Cohort 7, Cohort 8 |
| MEDI5752Also: volrustomigIntravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle | Drug | Cohort 10, Cohort 11, Cohort 9 |
| AZD7789Also: sabestomigIntravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle | Drug | Cohort 12, Cohort 13, Cohort 14 |
Primary outcome
Number of participants with DLTs; TEAEs and other safety parameters during the study.
Time frame: DLTs: within first cycle (21 days); TEAEs and other safety parameters: when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up (approximately 60 months)
DLTs, TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings
12 secondary outcomes
ORR as assessed by investigator per RECIST Version 1.1
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Duration of Response as assessed by investigator per RECIST version 1.1
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Disease Control Rate as assessed by the investigator per RECIST version 1.1
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Progression-free Survival as assessed by the investigator per RECIST v1.1
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Time to Response as assessed by investigator per RECIST Version 1.1
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Best percentage change in the Sum of Diameters of measurable tumors
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Overall Survival
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Pharmacokinetic Parameter Maximum Plasma/Serum Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a. Serum concentrations of durvalumab and MEDI5752, AZD2936, MEDI5752 and AZD7789.
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Pharmacokinetic Parameter Time to Maximum Plasma/Serum Concentration (Tmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Prevalence of Dato-Dxd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Incidence of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA
Time frame: At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Lung Cancer Study Locator details (for US)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
42 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Datopotamab deruxtecan, Durvalumab and Carboplatin in people with Advanced or Metastatic NSCLC, run by AstraZeneca at 42 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, Spain, Taiwan, Turkey (Türkiye), Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with DLTs; TEAEs and other safety parameters during the study. (time frame: DLTs: within first cycle (21 days); TEAEs and other safety parameters: when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up (approximately 60 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.