A Phase 1 interventional study of Datopotamab deruxtecan and Durvalumab in Advanced or Metastatic NSCLC, sponsored by AstraZeneca. Active, not recruiting at 42 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-27.
Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment
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).
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.
6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.
This study's enrollment of 155 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
Drug: Datopotamab deruxtecan · Drug: Durvalumab
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
Drug: Datopotamab deruxtecan · Drug: Durvalumab
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
Drug: Datopotamab deruxtecan · Drug: Durvalumab · Drug: Carboplatin
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
Drug: Datopotamab deruxtecan · Drug: Durvalumab · Drug: Carboplatin
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: AZD2936
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: AZD2936
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: Carboplatin · Drug: AZD2936
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: Carboplatin · Drug: AZD2936
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: Carboplatin · Drug: MEDI5752
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: Carboplatin · Drug: MEDI5752
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: MEDI5752
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
Drug: Datopotamab deruxtecan · Drug: AZD7789
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
Drug: Datopotamab deruxtecan · Drug: AZD7789
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: AZD7789
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC
Drug: Datopotamab deruxtecan · Drug: Durvalumab · Drug: Carboplatin
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Also known as: Dato-DXd
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Also known as: Imfinzi
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Also known as: rilvegostomig
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Also known as: volrustomig
Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle
Also known as: sabestomig
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
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)
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.
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
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.
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
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.
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
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
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 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)
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
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.
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
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
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.
Cmax = Maximum concentration
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.
Tmax = time to reach maximum concentration.
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.
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.
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
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)
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
ADA incidence is defined as the proportion of participants having treatment-emergent ADA during the study period
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).
Plan to share: 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
Supporting information: Study protocol, Sap, Csr
This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Carcinoma, Non-Small-Cell Lung→
AstraZeneca