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Combination treatment for advanced non-small cell lung cancer

A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07)

Phase 3 Interventional Daiichi Sankyo · NCT05555732

This study is testing whether a new combination of two treatments can help people with advanced lung cancer live longer and feel better compared to the standard chemotherapy options.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1170 (estimated)
Ages18 Years and up
SexAll
SponsorDaiichi Sankyo Industry-sponsored
Drugs / interventionsdatopotamab, pembrolizumab, chemotherapy
Locations240 sites (Daphne, Alabama and 239 other locations)
Trial IDNCT05555732 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of datopotamab deruxtecan (Dato-DXd) combined with pembrolizumab compared to pembrolizumab with pemetrexed and platinum chemotherapy in patients with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have not received prior therapy. Participants will be randomly assigned to one of three treatment groups to assess progression-free survival and overall survival. The study includes a screening period for eligibility, a treatment period, and a follow-up period to monitor outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced or metastatic non-squamous NSCLC and PD-L1 TPS less than 50%.

Not a fit: Patients with actionable genomic alterations or PD-L1 TPS of 50% or higher may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and quality of life for patients with advanced non-small cell lung cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and chemotherapy in lung cancer treatment.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

1. Sign and date the Main ICF, prior to the start of any study- specific qualification procedures. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
2. Adults ≥18 at the time the Main ICF is signed. (Follow local regulatory requirements if the legal age of adult voluntary consent for study participation is \>18 years old).
3. Has tumor with PD-L1 TPS \<50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of six slides). PD-L1 expression results available at the same central laboratory from screening for the purpose of entry into another Dato-DXd study may be used for tissue screening purposes in this study as long as the subject has not been randomized/enrolled in the other study.
4. Has provided a formalin-fixed tumor tissue sample (minimum of 4 × 4-micron sections or block equivalent) for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes. If a documented law or regulation prohibits (or does not approve) sample collection, then such sample will not be collected, and the subject is still eligible for the study.
5. Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Subjects who received adjuvant or neoadjuvant therapy other than those listed in the exclusion criteria are eligible if the adjuvant/ neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced/metastatic disease and should not have progressed on or within the 6 months of completion.
6. Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization.

Key Exclusion Criteria:

1. Has received prior systemic treatment for advanced/metastatic NSCLC.
2. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting (for NSCLC):

   1. Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
   2. TROP2-targeted therapy
   3. Any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
   4. Any other ICIs Subjects who received adjuvant or neoadjuvant therapy OTHER than those listed above are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced or metastatic disease.
3. Has received a live vaccine within 30 days prior to the first dose of study treatment.

   Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. For any subject receiving an approved severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine, please follow the vaccine label and/or local guidance. The vaccine manufacturer and the date of administration should be recorded on the electronic case report form (Concomitant Medications page), as should any AEs relating to the vaccine (including hypersensitivity or allergies). Note: Any licensed SARS-CoV2 vaccine (including those authorized for emergency use) in a particular country is allowed in the study as long as the vaccine is an mRNA vaccine, replication-incompetent adenoviral vaccine, or inactivated vaccine. Such vaccines will be treated just as any other concomitant therapy.

   Investigational vaccines (ie, those not licensed or authorized for emergency use) are not allowed.
4. Has spinal cord compression or clinically active untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 2 weeks by repeat imaging (Note: Repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 7 days before the first dose of study drug. Note: A contrasted computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain at baseline (MRI with contrast preferred) is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator must delay of study treatment to document stability of CNS metastases with repeat imaging at least 2 weeks later (in which case, repeat of all screening activity may be required).
5. Has uncontrolled or significant cardiovascular disease not controlled by maximal medical therapy, including:

   1. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval \>470 msec regardless of sex (based on the 12-lead electrocardiogram \[ECG\] performed at screening).
   2. Myocardial infarction within 6 months prior to Cycle 1 Day 1.
   3. History of a serious cardiac arrhythmia requiring treatment
   4. Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
   5. Left ventricular ejection fraction (LVEF) \<50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization.
   6. New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) at screening. Subjects with a history of Class II to IV CHF prior to screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
   7. Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg within 28 days before randomization that is not resolved despite maximal medical therapy).
6. Clinically severe pulmonary compromise as judged by the investigator resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli diagnosed within 3 months of Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc) or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), or prior complete pneumonectomy.

Where this trial is running

Daphne, Alabama and 239 other locations

+190 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 Metastatic Non Small Cell Lung CancerAdvanced Non Small Cell Lung CancerDatopotamab DeruxtecanPembrolizumabPemetrexedTropion-Lung07
Last reviewed 2026-06-13 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.