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Metastatic Lung CancerPhase 2ICARUS-LUNG01NCT04940325

Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer

A Phase 2 study testing DS-1062a in people with Metastatic Lung Cancer and Advanced Non Small Cell Lung Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 9 sites in France.

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 aims to evaluate the efficacy and safety of DS-1062a in participants with metastatic, unresectable NSCLC having progressed on one, but not more than three previous standard therapies. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DS-1062a
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
9 sitesFrance
Study dates
12 May 2021to Sep 2028
Phase
Phase 2
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

  • Participants with histologically confirmed diagnosis of advanced and/or unresectable NSCLC
  • Participants who received at least one line and not more than three lines of therapy and considered by the investigator as refractory to standard treatment or for which no standard treatment is available:
  • Participants who have no known mutation or mutation without an approved targeted therapy: anti programmed cell death (PD-1)/programmed death-ligand 1 (PD-L1) containing therapy and a platinum-doublet regimen
  • Participants who have known EGFR, BRAF, and MET mutation or ALK, ROS1, RET, NTRK fusion: one line of an approved targeted agent and one platinum-doublet regimen
  • Metastatic site easily accessible to biopsy (with exception of bone metastasis)
  • Presence of at least one measurable lesion (different from the biopsy site) according to RECIST v1.1
Show all 23Show fewer
  • ECOG status should be equal or less to one
  • Life expectancy should be equal or more than 3 months
  • Participants must have adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1, Day 1
  • Participants with asymptomatic and clinically stable treated brain metastasis, who require no treatment with corticosteroids and/or anticonvulsants. Participants must have a stable neurologic status for at least two weeks prior to Cycle 1 Day 1
  • Females of reproductive/childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception or avoid intercourse during the study and for at least 7 months after the last dose of study drug
  • Contraceptive methods considered highly effective:
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • Intrauterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomized partner
  • Complete sexual abstinence during and for at least 7 months after the last dose of study drug. Female participants must not donate, or retrieve for their own use, ova from the time of screening and for at least 7 months after the final study drug administration
  • Male participants must be surgically sterile or must withhold heterosexual intercourse or must be willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 4 months following the last dose of study drug.
  • Male participants must not freeze or donate sperm from screening and for at least 4 months after the final study drug administration.
  • Participants must understand, sign and date the written informed consent from prior to any protocol-specific procedures performed. Participants should be able and willing to comply with study visits and procedures as per protocol
  • Participants must be affiliated to a Social Security System or beneficiary of the same

Who cannot join

  • Participants unwilling to participate to the biological investigations and to perform biopsies and blood sample collection as required in the protocol
  • Participants with only bone metastasis will be excluded, except if they have an accessible primary tumor which could be biopsied at baseline, on-treatment and end-of-treatment.
  • Participant with any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening.
  • Participant with clinically severe pulmonary compromise (based on investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
  • Any underlying pulmonary disorder
  • Any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement
Show all 45Show fewer
  • OR prior pneumonectomy
  • Participants receiving chronic systemic corticosteroids at a dose higher than 10 mg prednisone or equivalent or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled steroids, or local steroid injections may be included in the study
  • Participants with evidence of any leptomeningeal disease
  • Participants with evidence of clinically active spinal cord compression or brain metastases
  • Participants with a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients (including but not limited to polysorbate 80) of DS-1062a
  • Participants with a history of severe hypersensitivity reactions to other monoclonal antibodies
  • Inadequate washout period prior to Cycle 1 Day 1, defined as:
  • Whole brain radiation therapy within 14 days before treatment or stereotactic brain radiation therapy, within 7 days before treatment
  • Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI)), within 14 days before treatment or 5 half-lives, whichever is longer
  • Immune checkpoint inhibitor therapy, within 21 days before treatment
  • Major surgery (excluding placement of vascular access), within 28 days before treatment
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation, within 28 days before treatment or palliative radiation therapy within 14 days before treatment
  • Chloroquine or hydroxychloroquine within 14 days before treatment
  • Live virus vaccination, within 28 days before treatment
  • Prior treatment with an anti-TROP-2 antibody including study drug
  • Participant previously treated with an antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I inhibitor
  • Participant with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved according to the NCI-CTCAE v5.0, grade 2 or more
  • Any evidence of primary malignancy other than locally advanced or metastatic lung cancer within three years prior to Cycle 1 Day 1, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated
  • Participant with clinically significant corneal disease
  • Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the investigator's opinion makes it undesirable for the participant to participate in the study or which would jeopardize compliance with the protocol
  • Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1, including:
  • Corrected QT interval higher than 470 ms for females and 450 ms for males according to Fridericia's formula (QTcF) and assessed based on triplicate ECGs, approximately 1 minute apart
  • Left ventricular ejection fraction (LVEF) less than 50% by either ECHO or Multigated Acquisition Scan (MUGA)
  • Uncontrolled hypertension (resting systolic blood pressure higher than 180 mmHg or diastolic blood pressure higher than 110 mmHg)
  • Myocardial infarction within six months
  • NYHA Classes 2 to 4 within 28 days before treatment
  • Uncontrolled angina pectoris within six months.
  • Cardiac arrhythmia requiring antiarrhythmic treatment. Patients with a history of cardiac arrythmia who, at baseline, are controlled with antiarrythmic treatments can be included.
  • Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1.
  • Participants with past or resolved hepatitis B virus (HBV) infection are eligible if:
  • Hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR
  • HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal transaminases (in the absence of liver metastasis); OR
  • HBsAg positive and HBV DNA viral load is documented to be equal or less than 2,000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with liver metastasis and abnormal transaminases AST/ALT less than 3 ULN
  • Participants with a history of Hepatitis C infection will be eligible for enrollment only if the viral load according to local standards of detection, is documented to be below the level of detection in the absence of anti-viral therapy during the previous 12 weeks (ie, sustained viral response according to the local product label but no less than 12 weeks, whichever is longer)
  • Participants with known human immunodeficiency virus (HIV) or active COVID-19 infection
  • Female participants who are pregnant or breastfeeding or intend to become pregnant during the study
  • Participants with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Participants under guardianship or deprived of his/her liberty by a judicial or administrative decision or incapable of giving his/her consent
  • Participation in another clinical trial evaluating an experimental drug (except non-interventional research)

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

France9 sites

  • Institut Bergonié

    Bordeaux, 33076

  • Institut de Cancérologie, CHRU Morvan de Brest

    Brest, 29200

  • Centre François Baclesse

    Caen, 14076

  • Centre Hospitalier Intercommunal de Créteil

    Créteil, 94010

  • Hôpital Cochin

    Paris, 75014

  • Hôpital Tenon

    Paris, 75970

  • Hospices Civils de Lyon - Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69310

  • Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67091

  • Gustave Roussy

    Villejuif, Villejuif, 94805

Other trials in France

About this study

Official title: Phase 2, Open Label Study of DS-1062a, an Anti-TROP-2-Antibody-Drug Conjugate (ADC), in Patients With Advanced and/or Unresectable Non-Small Cell Lung Cancer (NSCLC), With Biomarker Analysis to Characterize Response to Therapy

This study aims to evaluate the efficacy and safety of DS-1062a in participants with metastatic, unresectable NSCLC having progressed on one, but not more than three previous standard therapies. Moreover, the immune effects, the predictors of resistance and response to treatment, the effect of the chemotherapy on deoxyribonucleic acid (DNA) replication will be assessed and will help identify the subgroups that will mostly benefit from the treatment. The pharmacokinetics of the product and the anti-drug antibody (ADA) will be also evaluated.

A total of 100 participants are planned to be included in the study. Participants will receive, every three weeks, a dose of DS-1062a equivalent to 6 mg/kg of body weight until progression or until unacceptable toxicity.

Read more

Tumor evaluation will be performed every six weeks by the mean of a computed tomography for the thorax, abdomen and pelvis (TAP CT-scan) or a magnetic resonance imaging (MRI). Brain and/or bone CT scans will be also performed throughout the study for participants with brain and/or bone metastasis.

The safety of the product will be assessed, through complete clinical exams, biological tests, electrocardiograms (ECGs), cardiac echographies (ECHOs) and through the collection of ongoing toxicities or adverse events.

Being tested
DS-1062a
Keywords
Metastatic Lung Cancer, Advanced lung cancer, Antibody drug conjugate, ADC, Non small Cell lung Cancer, NSLC, Advanced non small Cell lung Cancer, Metastatic non small Cell lung Cancer, Datopotamab deruxtecan, Refractory NSCLC, Refractory Non small Cell lung Cancer, DS-1062, DS-1062a, unresectable lung cancer, unresectable non small Cell lung Cancer, Advanced NSCLC, Metastatic NSCLC, Unresectable NSCLC
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • DS-1062aDrug

    First infusion for 90 minutes and then infusion duration can be decreased to 30 minutes if participant didn't experience infusion related reactions (IRR)

Study groups in NCT04940325
Study groupRoleWhat they receive
DS-1062aExperimentalAll patients included in the study will receive DS-1062a at a dose of 6 mg/kg every 3 weeks until progression or until unacceptable toxicity
Receives: Drug: DS-1062a

What is being measured

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

  1. Evaluation of objective response rate (ORR) based on investigator assessment

    ORR is defined as the proportion of participants who achieved a confirmed complete response (CR) or partial response (PR) observed on treatment and assessed by investigators

    Measured: During treatment period, an average of 4 months

Secondary outcomes (9)

  1. Evaluation of duration of response (DoR)

    Defined as the time from the first documented CR or PR until the date of disease progression, or until the date of death

    Measured: From cycle 2 (Week 3) up to 3 years after the EoT, an average of 39 months]

  2. Evaluation of progression free Survival (PFS)

    Defined as the time date of the first dose until progression or death from any cause, whichever occurs first

    Measured: From cycle 2 (Week 3) up to 3 years after the EoT, an average of 39 months]

  3. Evaluation of clinical benefit ratio (CBR)

    Defined as the presence of at least a PR or CR, or a stable disease (SD) for more than six months under treatment

    Measured: From cycle 2 (Week 3) up to 3 years after the EoT, an average of 39 months]

  4. To evaluate incidence of adverse events (AEs)

    All adverse events (AEs), treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)

    Measured: During treatment (at each cycle), at EoT and up to 35 days after EoT, an average of 5 months]

  5. To evaluate proportion of treatment modification

    Treatment discontinuation, interruptions and dose reductions

    Measured: During treatment, an average of 4 months

  6. Incidence of abnormal laboratory test results

    Measured: During treatment (at each cycle) and at EoT, an average of 4 months

  7. To evaluate incidence of abnormal ECG readings

    Measured: During treatment (at each cycle) and at EoT, an average of 4 months

  8. To evaluate change in left ventricular ejection fraction (LVEF)

    Measured: During treatment and at EoT, an average of 4 months

  9. To assess changes in Eastern Cooperative Oncology Group performance status [ECOG PS] based on a score from 1 to 5, where higher scores mean worse outcomes

    Measured: During treatment (at each cycle) and at EoT, an average of 4 months

Timeline

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

  1. First posted25 Jun 2021
  2. Study start12 May 2021
  3. Primary completionApr 2028 (estimated)
  4. Study completionSep 2028 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
One group of 100 patients treated with DS-102a
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04940325
Sponsor's protocol ID
2023-505924-71-00
Other IDs
2020/3187, 2023
Acronym
ICARUS-LUNG01
Status last verified
Nov 2026
First submitted
3 Jun 2021
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Planchard D, Cozic N, Mosele MF, Corcos N, Le Bescond L, Pradat Y, Ghigna MR, Nachabeh G, Alfaro A, Catelain C, Job B, Mami-Chouaib F, Badel S, Corgnac S, Farace F, Oulhen M, Kannouche P, Ngoc Tran DT, Droin N, Wislez M, Chouaid C, Curcio H, Cousin S, Mascaux C, Cadranel J, Geier M, Cheikh-Hussin R, Guyader P, Signolle N, Godefroy K, Talbot H, Vakalopoulou M, Christodoulidis S, Bernard E, Koudou Y, Camara V, Belarkemi A, Klein A, Morretton JP, East P, Chiaverelli R, Zwirtes R, Michiels S, Barlesi F, Andre F, Montagnac G, Pistilli B. Efficacy, safety, and biomarker analysis of datopotamab deruxtecan in advanced non-small cell lung cancer: ICARUS-LUNG01 phase 2 study. Cancer Cell. 2026 Jun 8;44(6):1147-1159.e6. doi: 10.1016/j.ccell.2026.03.017. Epub 2026 Apr 17.

    PubMed 41999747

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DS-1062a in people with Metastatic Lung Cancer and Advanced Non Small Cell Lung Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 9 sites in France.

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 23 inclusion and 45 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 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Evaluation of objective response rate (ORR) based on investigator assessment (time frame: During treatment period, an average of 4 months). 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 NCT04940325, 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 6 Nov 2026.

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