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Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung04)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04612751
Recruitment Status : Recruiting
First Posted : November 3, 2020
Last Update Posted : May 19, 2023
Sponsor:
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This study will assess safety, tolerability, and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

Condition or disease Intervention/treatment Phase
Advanced or Metastatic NSCLC Drug: Datopotamab deruxtecan Drug: Durvalumab Drug: Carboplatin Drug: AZD2936 Drug: MEDI5752 Phase 1

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 who are either treatment-naïve or have received 1 prior line of systemic chemotherapy without concurrent ICI

Two dose levels of Dato-DXd will be studied in combination with fixed-dose of durvalumab, AZD2936, or MEDI5752, with or without 4 cycles of carboplatin in 11 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 232 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Dose escalation and dose expansion model
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 2, 2021
Estimated Primary Completion Date : February 28, 2025
Estimated Study Completion Date : February 28, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1
Datopotamab deruxtecan (Dato-DXd) + Durvalumab
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Imfinzi

Experimental: Cohort 2
Datopotamab deruxtecan (Dato-DXd) + Durvalumab
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Imfinzi

Experimental: Cohort 3
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Imfinzi

Drug: Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle

Experimental: Cohort 4
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Imfinzi

Drug: Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle

Experimental: Cohort 5
Datopotamab deruxtecan (Dato-DXd) + AZD2936
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: AZD2936
Intravenous infusion prior to Dato-DXd

Experimental: Cohort 6
Datopotamab deruxtecan (Dato-DXd) + AZD2936
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: AZD2936
Intravenous infusion prior to Dato-DXd

Experimental: Cohort 7
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle

Drug: AZD2936
Intravenous infusion prior to Dato-DXd

Experimental: Cohort 8
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle

Drug: AZD2936
Intravenous infusion prior to Dato-DXd

Experimental: Cohort 9
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle

Drug: MEDI5752
Intravenous infusion prior to Dato-DXd

Experimental: Cohort 10
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle

Drug: MEDI5752
Intravenous infusion prior to Dato-DXd

Experimental: Cohort 11
Datopotamab deruxtecan (Dato-DXd) + MEDI5752
Drug: Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
Other Name: Dato-DXd

Drug: MEDI5752
Intravenous infusion prior to Dato-DXd




Primary Outcome Measures :
  1. 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 55 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


Secondary Outcome Measures :
  1. 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 55 months). ]
    ORR is defined as the proportion of participants with measurable disease at baseline who achieved a BOR of confirmed CR or confirmed PR.

  2. 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 55 months). ]
    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.

  3. 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 55 months). ]
    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.

  4. 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 55 months). ]
    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

  5. 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 55 months). ]
    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)

  6. 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 55 months). ]
    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.

  7. 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 55 months). ]
    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

  8. Pharmacokinetic Parameter Maximum Plasma/Serum Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a and AZD2936. Serum concentrations of durvalumab and MEDI5752. [ 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 55 months). ]
    Cmax = Maximum concentration

  9. Pharmacokinetic Parameter Time to Maximum Plasma/Serum Concentration (Tmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a and AZD2936. Serum concentrations of durvalumab and MEDI5752. [ 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 55 months). ]
    Tmax = time to reach maximum concentration.

  10. Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, AZD2936, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion) [ 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 55 months). ]
    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.

  11. Prevalence of Dato-Dxd, durvalumab, AZD2936 and MEDI5752 [ 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 55 months). ]
    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)

  12. Incidence of Dato-DXd, durvalumab, AZD2936 and MEDI5752 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 55 months). ]
    ADA incidence is defined as the proportion of participants having treatment-emergent ADA during the study period



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 and no known genomic alterations in other actionable driver kinases with approved therapies
  • 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 5 to 11, participants must be treatment-naïve for advanced or metastatic NSCLC.
  • Willing and able to undergo a mandatory tumor biopsy
  • 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 11 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04612751


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Show Show 64 study locations
Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo, Inc.
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04612751    
Other Study ID Numbers: D926FC00001
2021-000274-28 ( EudraCT Number )
First Posted: November 3, 2020    Key Record Dates
Last Update Posted: May 19, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Advanced or Metastatic NSCLC
Datopotamab deruxtecan (Dato-DXd)
DS-1062a
Durvalumab
AZD2936
MEDI5752
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Durvalumab
Antineoplastic Agents
Antineoplastic Agents, Immunological