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

Study identifier:D926FC00001

ClinicalTrials.gov identifier:NCT04612751

EudraCT identifier:2021-000274-28

CTIS identifier:N/A

Recruiting

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)

Medical condition

Advanced or Metastatic NSCLC

Phase

Phase 1

Healthy volunteers

Study drug

Datopotamab deruxtecan, Durvalumab, Carboplatin, AZD2936, MEDI5752, AZD7789

Sex

All

Estimated Enrollment

321

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 02 Feb 2021

Estimated Primary Completion Date: 30 Jan 2026

Estimated Study Completion Date: 30 Jan 2026

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

Daiichi Sankyo

Inclusion and exclusion 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

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Arms	Assigned Interventions
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	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 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 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 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 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 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 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 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: AZD2936 Intravenous infusion prior to Dato-DXd Other Name: rilvegostomig
Experimental: Cohort 6 Datopotamab deruxtecan (Dato-DXd) + AZD2936 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: 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
Experimental: Cohort 8 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
Experimental: Cohort 9 Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + 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: MEDI5752 Intravenous infusion prior to Dato-DXd Other Name: volrustomig
Experimental: Cohort 10 Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + 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: MEDI5752 Intravenous infusion prior to Dato-DXd Other Name: volrustomig
Experimental: Cohort 11 Datopotamab deruxtecan (Dato-DXd) + MEDI5752 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: 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	Drug: AZD7789 Intravenous infusion prior to Dato-DXd Other Name: sabestomig
Experimental: Cohort 13 Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC	Drug: AZD7789 Intravenous infusion prior to Dato-DXd Other Name: sabestomig
Experimental: Cohort 14 Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC	Drug: AZD7789 Intravenous infusion prior to Dato-DXd Other Name: sabestomig

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]