Combining Dato-DXd with Immunotherapy for Advanced Lung Cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Research Site
  La Jolla, California, United States Recruiting
• Research Site
  Saint Louis, Missouri, United States Recruiting
• Research Site
  Lebanon, New Hampshire, United States Recruiting
• Research Site
  Hackensack, New Jersey, United States Recruiting
• Research Site
  Cleveland, Ohio, United States Recruiting
• Research Site
  Philadelphia, Pennsylvania, United States Recruiting

+18 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center
• Email: information.center@astrazeneca.com
• Phone: 1-877-240-9479

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Dato-DXd in solid tumors (Urothelial Cancer and KRAS-mutant NSCLC) in two sub-studies

  This study tests Datopotamab Deruxtecan (Dato-DXd) alone or with other cancer drugs in people with urothelial cancer or KRAS-mutant non-small cell lung cancer.

  Recruiting Phase 1/2 Daiichi Sankyo · Taichung · NCT07890714

• HS-10504 vs platinum-based chemotherapy in EGFR C797S+ NSCLC

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  Recruiting Phase 3 Jiangsu Hansoh Pharmaceutical Co., Ltd. · Guangzhou · NCT07754123

• Datopotamab deruxtecan versus docetaxel for previously treated TROP2-positive advanced non-squamous NSCLC

  This trial tests whether datopotamab deruxtecan works better than docetaxel for people with TROP2-positive advanced or metastatic non-squamous NSCLC who have already received prior therapy and do not have actionable genomic alterations.

  Recruiting at 182 sites Phase 3 AstraZeneca · Chandler, Arizona and 205 other locations · NCT07291037

• Preventing Dato‑DXd–related mouth sores with dexamethasone mouthwash

  This study will see if using an alcohol‑free dexamethasone mouthwash can prevent mouth sores in adults with advanced breast cancer or non‑squamous non‑small cell lung cancer who are receiving datopotumab deruxtecan.

  Recruiting Phase 2 Brown University · Providence, Rhode Island · NCT06974604

• Datopotamab deruxtecan with or without durvalumab for PD-L1–negative metastatic triple-negative breast cancer

  This will see if adding durvalumab to datopotamab deruxtecan helps people with PD-L1–negative advanced or metastatic triple-negative breast cancer live longer without their disease getting worse.

  Recruiting Phase 2 Queen Mary University of London · London and 1 other locations · NCT06954480

• Datopotamab-deruxtecan with carboplatin and pembrolizumab for treatment‑naive NSCLC that has spread to the brain

  This trial will try giving datopotamab-deruxtecan together with carboplatin and pembrolizumab to adults with metastatic non‑small cell lung cancer that has spread to the brain and has no targetable mutations.

  Recruiting at 13 sites Phase 2 Latin American Cooperative Oncology Group · Fortaleza, Ceará and 12 other locations · NCT06822543

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.