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Carcinoma, Non-Small-Cell LungPhase 2NCT06780085

A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01)

A Phase 2 study testing Raludotatug Deruxtecan, Ifinatamab Deruxtecan and Docetetaxel in people with Carcinoma, Non-Small-Cell Lung, run by Merck Sharp & Dohme LLC at 36 sites in 10 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

Researchers are looking for new ways to treat metastatic nonsquamous non-small cell lung cancer (NSCLC) that has been treated before. Metastatic means the cancer has spread to other parts of the body. Nonsquamous means the cancer did not start in squamous cells, which are flat cells that line the inside of the lungs. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Raludotatug Deruxtecan, Ifinatamab Deruxtecan and Docetetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
36 sitesin 10 countries
Study dates
13 May 2025to 12 Mar 2032
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

  • The main inclusion criteria include but are not limited to the following:
  • Histologically or cytologically confirmed diagnosis of Stage IV nonsquamous non-small cell lung cancer (NSCLC)
  • Documented disease progression per RECIST 1.1 after receiving an anti-programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) treatment and platinum-based chemotherapy
  • Confirmation per local test report that epidermal growth factor receptor negative (EGFR-), anaplastic lymphoma kinase negative (ALK-), c ros oncogene 1 negative (ROS1-), or other directed therapy is not indicated as primary therapy
  • Measurable disease per RECIST 1.1 as assessed by investigator and verified by BICR
  • Life expectancy of at least 3 months
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  • An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization
  • Is an individual of any sex/gender who is at least 18 years of age at the time of providing the informed consent
  • Has adequate organ function
  • If capable of producing sperm refrains from donating sperm plus either abstains from penile-vaginal intercourse or uses a penile/external condom, with contraceptive use consistent with local regulations
  • Participant/participants of childbearing potential (POCBP) is not pregnant and has a negative highly sensitive pregnancy test; and is not breastfeeding and uses a highly effective contraceptive method
  • Archival tumor tissue sample of a tumor lesion not previously irradiated has been provided
  • Has provided tissue prior to treatment randomization from a newly obtained formalin-fixed sample from a new biopsy
  • Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
  • Participants who are hepatitis B surface antigen (HBsAg) positive have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
  • Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

Who cannot join

  • The main exclusion criteria include but are not limited to the following:
  • Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
  • Received radiation therapy to the lung
  • Has uncontrolled or significant cardiovascular disorder prior to randomization
  • Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
  • Participants who have adverse events (AEs) (other than alopecia) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
Show all 25Show fewer
  • Has known severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients
  • Has clinically significant corneal disease
  • Has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids
  • Has inadequate washout period prior to randomization
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
  • Has previously received docetaxel as monotherapy or in combination with other therapies
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
  • Has known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has evidence of any leptomeningeal disease
  • Has history of interstitial lung disease (ILD)/pneumonitis, current diagnosis of ILD, and/or suspected ILD
  • Has active autoimmune disease that has required systemic treatment in the past 2 years
  • Has active infection requiring systemic therapy
  • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
  • Has known history of, or active, neurologic paraneoplastic syndrome
  • Has history of allogeneic tissue/solid organ transplant
  • Have not adequately recovered from major surgery or have ongoing surgical complications

Trial locations and contacts

36 sites in 10 countries.

36 sites in 10 countries

Israel6 sites

  • Rambam Health Care Campus ( Site 0076)

    Haifa, 3109601

  • Shaare Zedek Medical Center ( Site 0075)

    Jerusalem, 9103102

  • Meir Medical Center ( Site 0071)

    Kfar Saba, 4428164

  • Rabin Medical Center ( Site 0074)

    Petah Tikva, 4941492

  • Sheba Medical Center ( Site 0070)

    Ramat Gan, 5265601

  • Sourasky Medical Center ( Site 0077)

    Tel Aviv, 6423906

Other trials in Israel

Turkey (Türkiye)5 sites

  • Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 0141)

    Adana, 01250

  • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0140)

    Ankara, 06230

  • Ankara Bilkent Şehir Hastanesi. ( Site 0142)

    Ankara, 06800

  • I. U. Cerrahpasa Tip Fakultesi ( Site 0144)

    Istanbul, 34098

  • Ege Universitesi Hastanesi ( Site 0143)

    Izmir, 35100

Other trials in Turkey (Türkiye)

United States4 sites

  • MedStar Franklin Square Medical Center ( Site 0033)

    Baltimore, Maryland, 21237

  • Texas Oncology - DFW ( Site 8003)

    Dallas, Texas, 75246-2046

  • University of Kentucky Chandler Medical Center ( Site 0019)

    Lexington, Kentucky, 40536-0293

  • AHN Cancer Institute - Allegheny General ( Site 9501)

    Pittsburgh, Pennsylvania, 15212

Other trials in United States

Hungary4 sites

  • Petz Aladar Egyetemi Oktato Korhaz ( Site 0062)

    Győr, Győr-Moson-Sopron, 9024

  • Bacs-Kiskun Varmegyei Oktatokorhaz ( Site 0063)

    Kecskemét, Bács-Kiskun county, 6000

  • Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet ( Site 0061)

    Szolnok, Jász-Nagykun-Szolnok, 5000

  • Református Pulmonológiai Centrum ( Site 0064)

    Törökbálint, Pest County, 2045

Other trials in Hungary

Italy4 sites

  • Azienda Ospedaliera Universitaria Careggi ( Site 0173)

    Florence, 50134

  • Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175)

    Milan, Lombardy, 20133

  • Ospedale San Raffaele. ( Site 0171)

    Milan, 20132

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 0174)

    Roma, 00168

Other trials in Italy

Poland4 sites

  • Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)

    Gdansk, Pomeranian Voivodeship, 80-214

  • Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie ( Site 0152)

    Koszalin, West Pomeranian Voivodeship, 75-581

  • Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0153)

    Poznan, Greater Poland Voivodeship, 60-569

  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0151)

    Warsaw, Masovian Voivodeship, 02-781

Other trials in Poland

Chile3 sites

  • Centro de Estudios Clínicos SAGA ( Site 0161)

    Santiago, Region M. de Santiago, 7500653

  • Fundación Arturo López Pérez ( Site 0160)

    Santiago, Region M. de Santiago, 7500921

  • Bradfordhill ( Site 0162)

    Santiago, Region M. de Santiago, 8420383

Other trials in Chile

Germany2 sites

  • Charite-Universitaetsmedizin Berlin ( Site 0191)

    Berlin, 13353

  • Universitaetsklinik Tuebingen ( Site 0192)

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Greece2 sites

  • THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA"-3rd Dept of Internal Medicine and Laboratory, Oncol ( Site 0204)

    Athens, Attica, 115 27

  • European Interbalkan Medical Center ( Site 0205)

    Thessaloniki, 570 01

Other trials in Greece

Spain2 sites

  • Institut Català d'Oncologia - L'Hospitalet ( Site 0090)

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Universitario Quiron Madrid ( Site 0091)

    Madrid, 28223

Other trials in Spain

About this study

Official title: KEYMAKER-U01 Substudy 01H: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC)

Researchers are looking for new ways to treat metastatic nonsquamous non-small cell lung cancer (NSCLC) that has been treated before. Metastatic means the cancer has spread to other parts of the body. Nonsquamous means the cancer did not start in squamous cells, which are flat cells that line the inside of the lungs.

Standard treatment (usual treatment) for NSCLC is surgery, then immunotherapy with or without chemotherapy after surgery. Immunotherapy is a treatment that helps the immune system fight cancer. Chemotherapy is a medicine that works to destroy cancer cells or stop them from growing.

Read more

However, standard treatment may not work or may stop working for some people. Researchers want to know if 2 antibody drug conjugates (ADCs) can help treat metastatic nonsquamous NSCLC that did not respond (get smaller or go away) to treatment. An ADC attaches to specific targets on cancers cells and delivers treatment to destroy those cells.

Researchers will compare 2 different ADCs (the study treatments) to chemotherapy in this study. The goals of this study are to learn:

  • About the safety of the study treatments and if people tolerate them
  • How many people have the cancer respond to the study treatments
Read the detailed description

The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798

Being tested
Raludotatug Deruxtecan, Ifinatamab Deruxtecan, Docetetaxel, 5-hydroxytryptamine subtype 3 receptor antagonist, Neurokinin-1 receptor antagonist
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

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

  • Raludotatug DeruxtecanBiological

    Also called R-DXd, MK-5909, DS-6000a

    IV Infusion

  • Ifinatamab DeruxtecanBiological

    Also called I-DXd, MK-2400, DS-7300a

    IV Infusion

  • DocetetaxelDrug

    IV Infusion

  • 5-hydroxytryptamine subtype 3 receptor antagonistDrug

    Also called 5-HT3 receptor antagonist

    Administered as a rescue medication per approved product label before R-DXd or I-DXd infusion

  • Neurokinin-1 receptor antagonistDrug

    Also called NK-1 receptor antagonist

    Administered as a rescue medication per approved product label before R-DXd or I-DXd infusion

  • CorticosteroidDrug

    Administered as a rescue medication per approved product label before R-DXd or I-DXd infusion, and for 3 days starting 1 day prior to docetaxel administration

Study groups in NCT06780085
Study groupRoleWhat they receive
Raludotatug DeruxtecanExperimentalParticipants receive raludotatug deruxtecan (R-DXd) 5.6 mg/kg via intravenous (IV) Infusion every 3 weeks (q3w) until disease progression or discontinuation criterion is met.
Receives: Biological: Raludotatug Deruxtecan; Drug: 5-hydroxytryptamine subtype 3 receptor antagonist; Drug: Neurokinin-1 receptor antagonist; Drug: Corticosteroid
Ifinatamab DeruxtecanExperimentalParticipants receive ifinatamab deruxtecan (I-DXd) 12 mg/kg via IV infusion q3w until disease progression or discontinuation criterion is met.
Receives: Biological: Ifinatamab Deruxtecan; Drug: 5-hydroxytryptamine subtype 3 receptor antagonist; Drug: Neurokinin-1 receptor antagonist; Drug: Corticosteroid
DocetetaxelActive comparatorParticipants receive docetaxel 75mg/m2 via IV infusion q3w until disease progression or discontinuation criterion is met.
Receives: Drug: Docetetaxel; Drug: Corticosteroid

What is being measured

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

  1. Objective Response Rate (ORR)

    ORR is defined as the percentage of participants with Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

    Measured: Up to approximately 81 months

  2. Percentage of Participants with at Least One Adverse Event (AE)

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants who experience an AE will be reported.

    Measured: Up to approximately 81 months

  3. Percentage of Participants Who Discontinued Medication Due to an AE

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants who discontinue study intervention due to an AE will be reported.

    Measured: Up to approximately 24 months

Secondary outcomes (3)

  1. Duration of Response (DOR)

    For participants who demonstrate a confirmed CR (disappearance of all target lesions) or (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.

    Measured: Up to approximately 81 months

  2. Progression-free Survival (PFS)

    PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.

    Measured: Up to approximately 81 months

  3. Overall Survival (OS)

    OS is defined as the time from randomization to death due to any cause.

    Measured: Up to approximately 81 months

Timeline

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

  1. First posted17 Jan 2025
  2. Study start13 May 2025
  3. Primary completion12 Mar 2032 (estimated)
  4. Study completion12 Mar 2032 (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
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
96 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06780085
Sponsor's protocol ID
3475-01H
Other IDs
2024-518761-10-00, MK-3475-01H, U1111-1314-1785, KEYMAKER-U01
Status last verified
Nov 2026
First submitted
13 Jan 2025
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Raludotatug Deruxtecan, Ifinatamab Deruxtecan and Docetetaxel in people with Carcinoma, Non-Small-Cell Lung, run by Merck Sharp & Dohme LLC at 36 sites in 10 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 16 inclusion and 25 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 36 sites in Israel, Turkey (Türkiye), United States, Hungary, Italy and 5 more countries. 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?

Objective Response Rate (ORR) (time frame: Up to approximately 81 months). The study lists 3 primary outcomes in all. 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 NCT06780085.

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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