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AzTrials

Lung NeoplasmPhase 2NCT06780098

Substudy 01I: A Study of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01I/KEYMAKER-U01I)

A Phase 2 study testing R-DXD, I-DXD and Docetaxel in people with Lung Neoplasm, run by Merck Sharp & Dohme LLC at 46 sites in 11 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Researchers are looking for other ways to treat metastatic squamous non-small cell lung cancer (NSCLC). Squamous NSCLC is cancer that starts in squamous cells, which are flat cells that line the inside of the airways in the lungs. Metastatic means the cancer has spread to other parts of the body. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Neoplasm
What is being tested?
R-DXD, I-DXD and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
144 participants
Where
46 sitesin 11 countries
Study dates
28 May 2025to 2 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 squamous non-small cell lung cancer (NSCLC)
  • Has documented disease progression per Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1), as assessed by investigator after receiving an anti-programmed cell death protein 1 (anti-PD-1)/programmed cell death ligand 1 (PD-L1) treatment and platinum-based chemotherapy for Stage IV disease
  • Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
  • Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
  • Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

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
  • Has uncontrolled or significant cardiovascular disorder
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc), or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc), or prior pneumonectomy
  • Participants who have adverse events (AEs) (other than alopecia) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
  • Has clinically significant corneal disease
Show all 18Show fewer
  • Has previously received docetaxel as monotherapy or in combination with other therapies
  • 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
  • Evidence of any leptomeningeal disease
  • Has one or more of the following indicators of interstitial lung disease (ILD)/pneumonitis: any history of ILD/pneumonitis irrespective of steroid use (except for a history of radiation pneumonitis that did not require steroids), current diagnosis of ILD, clinical or radiographic suspicion of ILD
  • Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
  • Active infection requiring systemic therapy
  • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
  • Known history of, or active, neurologic paraneoplastic syndrome
  • History of allogeneic tissue/solid organ transplant
  • Has not adequately recovered from major surgery or have ongoing surgical complications

Trial locations and contacts

46 sites in 11 countries. Contact the study team or a site near you to ask about taking part.

Toll Free Number contact

1-888-577-8839

Trialsites@msd.com

46 sites in 11 countries

China8 sites, 8 recruiting

  • Beijing Cancer Hospital ( Site 0301)

    Beijing, Beijing Municipality, 100142

    Study Coordinator, 010-88121122

    Recruiting

  • Chongqing University Cancer Hospital ( Site 0304)

    Chongqing, Chongqing Municipality, 400030

    Study Coordinator, +86023-65311341

    Recruiting

  • Fujian Provincial Cancer Hospital ( Site 0310)

    Fuzhou, Fujian, 350014

    Study Coordinator, 0591-83660063

    Recruiting

  • Nanjing Drum Tower Hospital JiangBei International Branch Hospital ( Site 0309)

    Nanjing, Jiangsu, 210008

    Study Coordinator, +86021-65115006

    Recruiting

  • Guangxi Medical University Cancer Hospital ( Site 0303)

    Nanning, Guangxi, 530201

    Study Coordinator, 0771-5323175

    Recruiting

  • Shanghai Chest Hospital ( Site 0308)

    Shanghai, Shanghai Municipality, 200030

    Study Coordinator, 021-63846590

    Recruiting

  • Shanghai Pulmonary Hospital ( Site 0300)

    Shanghai, Shanghai Municipality, 200433

    Study Coordinator, 021-65115006

    Recruiting

  • Henan Cancer Hospital ( Site 0311)

    Zhengzhou, Henan, 450000

    Study Coordinator, +8613837174273

    Recruiting

Other trials in China

Israel6 sites, 6 recruiting

  • Rambam Health Care Campus ( Site 0076)

    Haifa, 3109601

    Study Coordinator, +972 47776234

    Recruiting

  • Shaare Zedek Medical Center ( Site 0075)

    Jerusalem, 9103102

    Study Coordinator, +972-2-6555768

    Recruiting

  • Meir Medical Center ( Site 0071)

    Kfar Saba, 4428164

    Study Coordinator, +97297472414

    Recruiting

  • Rabin Medical Center ( Site 0074)

    Petah Tikva, 4941492

    Study Coordinator, +97239378101

    Recruiting

  • Sheba Medical Center ( Site 0070)

    Ramat Gan, 5265601

    Study Coordinator, +97235307032

    Recruiting

  • Sourasky Medical Center ( Site 0077)

    Tel Aviv, 6423906

    Study Coordinator, +972-3-6973082

    Recruiting

Other trials in Israel

Turkey (Türkiye)5 sites, 5 recruiting

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

    Adana, 01250

    Study Coordinator, +905353067506

    Recruiting

  • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0140)

    Ankara, 06230

    Study Coordinator, +90 312 305 43 36

    Recruiting

  • Ankara Bilkent Şehir Hastanesi. ( Site 0142)

    Ankara, 06800

    Study Coordinator, +903125529999

    Recruiting

  • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0144)

    Istanbul, 34098

    Study Coordinator, +902124143000

    Recruiting

  • Ege Universitesi Hastanesi ( Site 0143)

    Izmir, İzmir, 35100

    Study Coordinator, +90 232 343 43 43

    Recruiting

Other trials in Turkey (Türkiye)

United States4 sites, 4 recruiting

  • MedStar Franklin Square Medical Center ( Site 0033)

    Baltimore, Maryland, 21237

    Study Coordinator, 443-777-7147

    Recruiting

  • Texas Oncology - DFW ( Site 8003)

    Dallas, Texas, 75246-2046

    Study Coordinator, 214-370-1067

    Recruiting

  • Virginia Cancer Specialists (VCS) ( Site 0408)

    Fairfax, Virginia, 22031

    Study Coordinator, 703-280-5390

    Recruiting

  • University of Kentucky Chandler Medical Center ( Site 0019)

    Lexington, Kentucky, 40536-0293

    Study Coordinator, 859-257-1000

    Recruiting

Other trials in United States

Italy4 sites, 4 recruiting

  • Azienda Ospedaliera Universitaria Careggi ( Site 0173)

    Florence, 50134

    Study Coordinator, +393209225506

    Recruiting

  • IRCCS Ospedale San Raffaele ( Site 0171)

    Milan, 20132

    Study Coordinator, +390223903829

    Recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175)

    Milan, 20133

    Study Coordinator, 390223902190

    Recruiting

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

    Roma, 00168

    Study Coordinator, +390630156318

    Recruiting

Other trials in Italy

Poland4 sites, 4 recruiting

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

    Gdansk, Pomeranian Voivodeship, 80-214

    Study Coordinator, +48585844466

    Recruiting

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

    Koszalin, West Pomeranian Voivodeship, 75-581

    Study Coordinator, +48943488930

    Recruiting

  • Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0153)

    Poznan, Greater Poland Voivodeship, 60-569

    Study Coordinator, +48616654242

    Recruiting

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

    Warsaw, Masovian Voivodeship, 02-781

    Study Coordinator, +48225463066

    Recruiting

Other trials in Poland

Spain4 sites, 4 recruiting

  • Hospital Clinic de Barcelona ( Site 0092)

    Barcelona, Catalonia, 08036

    Study Coordinator, 34 932275402

    Recruiting

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

    L'Hospitalet de Llobregat, Barcelona, 08908

    Study Coordinator, 0034932607744

    Recruiting

  • Hospital Universitario Quiron Madrid ( Site 0091)

    Madrid, 28223

    Study Coordinator, 34914521987

    Recruiting

  • Hospital Universitario Virgen Macarena ( Site 0094)

    Seville, 41009

    Study Coordinator, +34 671560092

    Recruiting

Other trials in Spain

Chile3 sites, 3 recruiting

  • Centro de Estudios Clínicos SAGA ( Site 0161)

    Santiago, Region M. de Santiago, 7500653

    Study Coordinator, +56991612199

    Recruiting

  • Fundación Arturo López Pérez ( Site 0160)

    Santiago, Region M. de Santiago, 7500921

    Study Coordinator, 56227128000

    Recruiting

  • Bradfordhill ( Site 0162)

    Santiago, Region M. de Santiago, 8420383

    Study Coordinator, +56229490970

    Recruiting

Other trials in Chile

Greece3 sites, 3 recruiting

  • THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA" ( Site 0204)

    Athens, Attica, 115 27

    Study Coordinator, 0030 2107700220

    Recruiting

  • F. THERAPIS GENERAL ( Site 0206)

    Athens, Attica, 116 34

    Study Coordinator, +302107291111

    Recruiting

  • European Interbalkan Medical Center-Oncology Department ( Site 0205)

    Thessaloniki, 570 01

    Study Coordinator, 0030 2310400213

    Recruiting

Other trials in Greece

Hungary3 sites, 3 recruiting

  • Petz Aladar Egyetemi Oktato Korhaz ( Site 0062)

    Győr, Győr-Moson-Sopron, 9024

    Study Coordinator, +3696507900

    Recruiting

  • Bacs-Kiskun Varmegyei Oktatokorhaz ( Site 0063)

    Kecskemét, Bács-Kiskun county, 6000

    Study Coordinator, +3676516700

    Recruiting

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

    Szolnok, Jász-Nagykun-Szolnok, 5000

    Study Coordinator, +3656503603

    Recruiting

Other trials in Hungary

Germany2 sites, 2 recruiting

  • Charite-Universitaetsmedizin Berlin ( Site 0191)

    Berlin, 13353

    Study Coordinator, +49 30 450 553 044

    Recruiting

  • UniversitaetsklInikum Tuebingen ( Site 0192)

    Tübingen, Baden-Wurttemberg, 72076

    Study Coordinator, +4970712982795

    Recruiting

Other trials in Germany

About this study

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

Researchers are looking for other ways to treat metastatic squamous non-small cell lung cancer (NSCLC). Squamous NSCLC is cancer that starts in squamous cells, which are flat cells that line the inside of the airways in the lungs. Metastatic means the cancer has spread to other parts of the body.

Standard treatment (usual treatment) for metastatic squamous NSCLC is immunotherapy with or without chemotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing. However, standard treatment may not work or may stop working to treat metastatic squamous NSCLC.

Read more

Researchers want to learn if study treatments that are antibody drug conjugates (ADCs) can treat metastatic squamous NSCLC that did not respond (get smaller or go away) to standard treatment. An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells.

The main goals of this study are to learn about:

  • The cancer response to the study treatments compared to chemotherapy
  • The safety of the study treatments and if people tolerate them

This study is one of the substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Read the detailed description

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

Conditions
Lung Neoplasm
Being tested
R-DXD, I-DXD, Docetaxel, Rescue Medications, Rescue Medication
Medical subject headings
Lung Neoplasms

What participants receive

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

  • R-DXDBiological

    Also called Raludotatug deruxtecan, MK-5909, DS-6000a

    IV Infusion

  • I-DXDBiological

    Also called Ifinatamab deruxtecan, MK-2400, DS-7300a

    IV Infusion

  • DocetaxelDrug

    Also called Taxotere®

    IV Infusion

  • Rescue MedicationsDrug

    Participants receive rescue medications consisting of a combination regimen to include corticosteroids with a 5-hydroxytryptamine subtype 3 receptor antagonist and/or a neurokinin-1 receptor antagonist, all per approved product label and following institutional standards or local guidelines.

  • Rescue MedicationDrug

    Participants are premedicated with corticosteroids per approved product label and following institutional standards or local guidelines.

Study groups in NCT06780098
Study groupRoleWhat they receive
Arm 1: Raludotatug deruxtecan (R-DXD)ExperimentalParticipants receive 5.6 mg/kg of R-DXD, every 3 weeks (Q3W) (Day 1 of every 21-day cycle) via intravenous (IV) infusion until progressive disease (PD) or discontinuation.
Receives: Biological: R-DXD; Drug: Rescue Medications
Arm 2: Infinatamab deruxtecan (I-DXD) High DoseExperimentalParticipants receive 12 mg/kg of I-DXD, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Receives: Biological: I-DXD; Drug: Rescue Medications
Arm 3: I-DXD Low DoseExperimentalParticipants receive 8 mg/kg of I-DXD, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Receives: Biological: I-DXD; Drug: Rescue Medications
Arm 4: DocetaxelActive comparatorParticipants receive 75 mg/m^2 of Docetaxel, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.
Receives: Drug: Docetaxel; Drug: Rescue Medication

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 Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) as assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR will be assessed by Blinded Independent Central Review (BICR). The percentage of participants who experience CR or PR as assessed by the investigator will be presented.

    Measured: Up to approximately 81 months

  2. Number of participants who experience one or more adverse events (AEs)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.

    Measured: Up to approximately 81 months

  3. Number of participants who discontinue study intervention due to an AE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported.

    Measured: Up to approximately 81 months

Secondary outcomes (3)

  1. Duration of Response (DOR)

    For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (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 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 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 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 start28 May 2025
  3. Primary completion2 Mar 2032 (estimated)
  4. Study completion2 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
144 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06780098
Sponsor's protocol ID
3475-01I
Other IDs
MK-3475-01I, U1111-1314-2392, 2024-518839-11-00, KEYMAKER-01I
Status last verified
Oct 2026
First submitted
13 Jan 2025
Last updated
7 Oct 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 R-DXD, I-DXD and Docetaxel in people with Lung Neoplasm, run by Merck Sharp & Dohme LLC at 46 sites in 11 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 6 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in China, Israel, Turkey (Türkiye), United States, Italy and 6 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?

Contact Toll Free Number (1-888-577-8839, Trialsites@msd.com), or a site near the patient. 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 NCT06780098.

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 7 Oct 2026; AzTrials last refreshed its copy on 2 Nov 2026.

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