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Advanced or Metastatic NSCLCPhase 1NCT04526691

Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02)

A Phase 1 study testing Datopotamab deruxtecan, KEYTRUDA® and Carboplatin in people with Advanced or Metastatic NSCLC, run by Daiichi Sankyo at 24 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic non-small cell lung cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced or Metastatic NSCLC
What is being tested?
Datopotamab deruxtecan, KEYTRUDA® and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
24 sitesin 5 countries
Study dates
15 Sep 2020to 31 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed at diagnosis of NSCLC that:
  • Is advanced or metastatic.
  • Participants with non-squamous histology must have documented negative test results for actionable EGFR and ALK genomic alterations. Participants with squamous histology are required to undergo testing for EGFR and ALK genomic alterations if they are nonsmokers or under the age of 40 years.
  • Has either documented negative or unknown test results for actionable genomic alterations in ROS1, NTRK, BRAF, RET, MET, or other actionable oncogenic driver kinases.
  • Participants with tumors that harbor KRAS mutations are eligible for this study.
  • Participants with non-actionable genomic alterations in EGFR, ALK, ROS1, NTRK, BRAF, RET, MET, or other kinases are eligible for the study.
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  • Documentation of radiological disease progression while on or after receiving the most recent treatment regimen, if any, for advanced or metastatic NSCLC.
  • Must meet the following prior therapy requirements for advanced or metastatic NSCLC:
  • Dose escalation (all cohorts): Has received ≤2 lines of prior anticancer therapy for locally advanced or metastatic NSCLC.
  • Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab): Has not received PD-1/PD-L1, PD-L2, CTLA-4 directed immunotherapy and may or may not have been treated with systemic chemotherapy for advanced or metastatic NSCLC.
  • Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 200 mg fixed dose of pembrolizumab and 4 cycles of AUC 5 carboplatin or cisplatin 75 mg/m^2): Has not been treated with systemic anticancer therapy for advanced or metastatic NSCLC.
  • Willing and able to undergo a mandatory tumor biopsy.
  • Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue is available, for measurement of TROP2 expression levels or other biomarkers.
  • Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 Day 1.
  • Is not a candidate for surgical resection or chemoradiation with curative intent.

Who cannot join

  • Experienced grade 3 or higher immune-related adverse events (AEs) with prior treatment of anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 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, OX 40, CD137).
  • Received a live vaccine within 30 days prior to the first dose of study treatment.
  • Active, known, or suspected autoimmune disease.
  • Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications, except for managing AEs.
  • Prior organ transplantation, including allogeneic tissue or solid organ transplantation.
  • Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
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  • History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
  • History of another primary malignancy (beyond NSCLC) except for:
  • Malignancy treated with curative intent and with no known active disease for ≥3 years.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated carcinoma in situ without evidence of disease.
  • Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression.

Trial locations and contacts

24 sites in 5 countries.

24 sites in 5 countries

United States9 sites

  • Johns Hopkins Kimmel Cancer Center at Bayview

    Baltimore, Maryland, 21224

  • The Skip Viragh Outpatient Cancer Building

    Baltimore, Maryland, 21287

  • City of Hope

    Duarte, California, 91010

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • NEXT Oncology

    San Antonio, Texas, 78229

  • Quantum Santa Fe

    Santa Fe, New Mexico, 87505

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • Johns Hopkins Kimmel Cancer Center

    Washington D.C., District of Columbia, 20016

Other trials in United States

Spain5 sites

  • H. Vall Hebrón (Vall Hebron Institut de Oncologia - VHIO)

    Barcelona, 08035

  • START Madrid - Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • (CIOCC-START) Hospital Universitario HM Sanchinarro

    Madrid, 28050

  • Hospital Puerta de Hierro

    Majadahonda, 28222

Other trials in Spain

Taiwan4 sites

  • Chung Shan Medical University Hospital

    Taichung, 40201

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Cheng Kung University Hospital NCKUH

    Tainan, 704

  • National Taiwan University Hospital NTUH

    Taipei, 100

Other trials in Taiwan

Italy3 sites

  • Instituto Europeo Di Oncologica

    Milan, 20141

  • Azienda Ospedaliera San Gerardo

    Monza, 20052

  • Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Struttura di Oncologia

    Naples, 80131

Other trials in Italy

Japan3 sites

  • National Cancer Center Hospital East

    Chiba, 277-8577

  • National Cancer Center Hospital

    Tokyo, 104-0045

  • Showa Medical University Hospital

    Tokyo, 142-8555

Other trials in Japan

About this study

Official title: Phase 1b, Multicenter, Open-label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02)

This study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic non-small cell lung cancer.

Read the detailed description

The primary objective of this study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without 4 cycles of platinum chemotherapy in participants with advanced or metastatic NSCLC who have either been previously treated or are treatment naïve in a metastatic setting.

Two dose levels of Dato-DXd (4.0 mg/kg and 6.0 mg/kg) will be studied in combination with 200 mg fixed-dose pembrolizumab in 6 study cohorts. This study will be conducted sequentially and dose escalation will occur according to lower dose to higher dose in the same combination regimen (4.0 mg/kg to 6.0 mg/kg) and from 2-drug combination (Dato-DXd and pembrolizumab) to 3-drug combination regimen (Dato-DXd, pembrolizumab, and carboplatin or cisplatin).

Being tested
Datopotamab deruxtecan, KEYTRUDA®, Carboplatin, Cisplatin
Keywords
Advanced or Metastatic NSCLC, Datopotamab deruxtecan (Dato-DXd), Pembrolizumab, KEYNOTE, DS-1062a
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Datopotamab deruxtecanDrug

    Also called Dato-DXd

    Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle (starting datopotamab deruxtecan dose of 4.0 mg/kg)

  • KEYTRUDA®Drug

    Also called pembrolizumab

    Intravenous infusion Q3W on Day 1 of each 21-day cycle (fixed pembrolizumab dose 200 mg Q3W)

  • CarboplatinDrug

    Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (AUC 5)

  • CisplatinDrug

    Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle (75 mg/m^2)

Study groups in NCT04526691
Study groupRoleWhat they receive
Datopotamab deruxtecan (Dato-DXd)ExperimentalDose Escalation and Dose Expansion: Datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic NSCLC
Receives: Drug: Datopotamab deruxtecan; Drug: KEYTRUDA®; Drug: Carboplatin; Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with Dose-limiting Toxicities (DLTs) and Treatment-emergent Adverse Events (TEAEs)

    Measured: Baseline up to Cycle 1 (Days 1 to 21) for DLTs and up to 28 days after last dose for TEAEs, up to approximately 30 months post-dose

Secondary outcomes (8)

  1. Objective Response Rate

    Measured: Baseline up to BOR (confirmed CR or PR), up to approximately 30 months post-dose

  2. Duration of Response

    Measured: From first objective response (confirmed CR or PR) to PD or death (whichever occurs first), up to approximately 30 months post-dose

  3. Progression-free Survival

    Measured: Baseline up PD or death (whichever occurs first), up to approximately 30 months post-dose

  4. Overall Survival

    Measured: Baseline up to death (any cause), up to approximately 30 months post-dose

  5. Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a

    Measured: Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days)

  6. Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a

    Measured: Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days)

  7. Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total Anti-TROP2 Antibody, and MAAA-1181a

    Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.

    Measured: Cycle 1, Day 1: pre-dose, 30 minutes, 3 hours, 5 hours, and 7 hours post-dose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: pre-dose and post-dose (each cycle is 21 days)

  8. Anti-drug Antibodies for Dato-DXd and Pembrolizumab

    Measured: Baseline up to approximately 30 months post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2020
  2. Study start15 Sep 2020
  3. Primary completion14 Apr 2024
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Dose escalation and dose expansion model
Masking
None (open label)
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04526691
Sponsor's protocol ID
DS1062-A-U102
Other IDs
2020-006047-25, jRCT2031200193, KEYNOTE-B43, MK-3475-B43
Status last verified
May 2026
First submitted
21 Aug 2020
Last updated
15 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Publications

  • Levy B, Paz-Ares L, Lin CC, Herbert S, Yang TY, Tolcher A, Lou Y, Zenke Y, Cortinovis D, Felip E, Domine M, Leventakos K, Calvo E, Horiike A, Pan E, Basak P, Lin D, Gu W, Chiaverelli R, Chisamore MJ, Goto Y. Datopotamab Deruxtecan Plus Pembrolizumab With or Without Platinum-Based Chemotherapy for Advanced or Metastatic NSCLC: The Phase Ib TROPION-Lung02 Trial. J Thorac Oncol. 2026 Jul;21(7):103688. doi: 10.1016/j.jtho.2026.103688. Epub 2026 Mar 21.

    PubMed 41871716

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Datopotamab deruxtecan, KEYTRUDA® and Carboplatin in people with Advanced or Metastatic NSCLC, run by Daiichi Sankyo at 24 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Spain, Taiwan, Italy, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Dose-limiting Toxicities (DLTs) and Treatment-emergent Adverse Events (TEAEs) (time frame: Baseline up to Cycle 1 (Days 1 to 21) for DLTs and up to 28 days after last dose for TEAEs, up to approximately 30 months post-dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04526691, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.

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