Trial record 1 of 1 for:
D926FC00001
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)
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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 |
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Recruitment Status :
Recruiting
First Posted : November 3, 2020
Last Update Posted : March 18, 2024
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Sponsor:
AstraZeneca
Collaborator:
Daiichi Sankyo
Information provided by (Responsible Party):
AstraZeneca
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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 Drug: AZD7789 | Phase 1 |
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 14 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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 321 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 : | January 30, 2026 |
| Estimated Study Completion Date : | January 30, 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
Drug Information
available for:
Carboplatin
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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
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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 |
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Experimental: 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
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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 |
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Experimental: 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
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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 |
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Experimental: 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
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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 |
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Experimental: Cohort 5
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
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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
Other Name: rilvegostomig |
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Experimental: Cohort 6
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
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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
Other Name: rilvegostomig |
|
Experimental: Cohort 7
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
|
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
Other Name: rilvegostomig |
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Experimental: Cohort 8
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
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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
Other Name: rilvegostomig |
|
Experimental: Cohort 9
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
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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
Other Name: volrustomig |
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Experimental: Cohort 10
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
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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
Other Name: volrustomig |
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Experimental: Cohort 11
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC
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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
Other Name: volrustomig |
|
Experimental: Cohort 12
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
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Drug: AZD7789
Intravenous infusion prior to Dato-DXd
Other Name: sabestomig |
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Experimental: Cohort 13
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
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Drug: AZD7789
Intravenous infusion prior to Dato-DXd
Other Name: sabestomig |
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Experimental: Cohort 14
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC
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Drug: AZD7789
Intravenous infusion prior to Dato-DXd
Other Name: sabestomig |
Primary Outcome Measures :
- 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 :
- 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.
- 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.
- 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.
- 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
- 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)
- 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.
- 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
- 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 55 months). ]Cmax = Maximum concentration
- 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 55 months). ]Tmax = time to reach maximum concentration.
- 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 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.
- 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 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)
- 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 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.
| 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 (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 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
- 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
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
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 68 study locations
Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo
| 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: | March 18, 2024 |
| Last Verified: | March 2024 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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Advanced or Metastatic NSCLC Datopotamab deruxtecan (Dato-DXd) DS-1062a Durvalumab |
AZD2936 MEDI5752 AZD7789 |
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 |