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Combining Dato-DXd with Immunotherapy for Advanced Lung Cancer

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)

Phase 1 Interventional AstraZeneca · NCT04612751

This study is testing a new combination of a lung cancer drug and immunotherapy to see if it helps people with advanced non-small cell lung cancer feel better and live longer.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment371 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionschemotherapy, datopotamab, immunotherapy, durvalumab
Locations68 sites (Duarte, California and 67 other locations)
Trial IDNCT04612751 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of datopotamab deruxtecan (Dato-DXd) when combined with immunotherapy, with or without carboplatin, in patients with advanced or metastatic non-small cell lung cancer (NSCLC). It involves multiple cohorts where participants will receive different doses of Dato-DXd alongside various immunotherapy agents. The study will assess dose-limiting toxicities and may expand to further cohorts based on initial findings. The goal is to determine the best treatment combinations for this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced or metastatic NSCLC who have not had certain genomic alterations and have limited prior treatment.

Not a fit: Patients with EGFR or ALK genomic alterations or those who have had multiple lines of prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new effective treatment option for patients with advanced or metastatic NSCLC.

How similar studies have performed: Other studies have shown promise in combining immunotherapy with novel agents, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / 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 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

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

Where this trial is running

Duarte, California and 67 other locations

+18 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced or Metastatic NSCLCDatopotamab deruxtecanDS-1062aDurvalumabAZD2936MEDI5752AZD7789
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.