ACTIVE_NOT_RECRUITING

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

Conditions

Advanced or Metastatic NSCLC Datopotamab deruxtecan (Dato-DXd)DS-1062a Durvalumab AZD2936 MEDI5752 AZD7789

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

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)

Quick Facts

Study Start:2021-02-02

Study Completion:2026-04-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04612751

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 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	* 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

Inclusion Criteria

Exclusion 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 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

* 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

Contacts and Locations

Study Locations (Sites)

Research Site

La Jolla, California, 92093

United States

Research Site

Santa Ana, California, 92705

United States

Research Site

St Louis, Missouri, 63110

United States

Research Site

Hackensack, New Jersey, 07601

United States

Research Site

Cleveland, Ohio, 44106

United States

Research Site

Philadelphia, Pennsylvania, 19111

United States

Research Site

Dallas, Texas, 75230

United States

Research Site

Houston, Texas, 77030

United States

Research Site

San Antonio, Texas, 78229

United States

Research Site

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-02-02

Study Completion Date2026-04-30

Study Record Updates

Study Start Date2021-02-02

Study Completion Date2026-04-30

Terms related to this study

Keywords Provided by Researchers

Advanced or Metastatic NSCLC
Datopotamab deruxtecan (Dato-DXd)
DS-1062a
Durvalumab
AZD2936
MEDI5752
AZD7789

Additional Relevant MeSH Terms

Advanced or Metastatic NSCLC