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

NCT06780085 | Recruiting Phase 2 FDA Drug

• 5 other identifiers: 3475-01H2024-518761-10-00MK-3475-01HU1111-1314-1785KEYMAKER-U01
• Study Type: interventional
• Target: 96
• Locations: 10 countries
• Sites: 32

Brief 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. 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. 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

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to approximately 81 months

• 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.

  Up to approximately 81 months

• 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.

  Up to approximately 24 months

Secondary Outcomes (3)

• Duration of Response (DOR)

  Up to approximately 81 months

• Progression-free Survival (PFS)

  Up to approximately 81 months

• Overall Survival (OS)

  Up to approximately 81 months

Study Arms (3)

Raludotatug Deruxtecan

EXPERIMENTAL

Participants 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.

Biological: Raludotatug Deruxtecan; Drug: 5-hydroxytryptamine subtype 3 receptor antagonist; Drug: Neurokinin-1 receptor antagonist; Drug: Corticosteroid

Ifinatamab Deruxtecan

EXPERIMENTAL

Participants receive ifinatamab deruxtecan (I-DXd) 12 mg/kg via IV infusion q3w until disease progression or discontinuation criterion is met.

Biological: Ifinatamab Deruxtecan; Drug: 5-hydroxytryptamine subtype 3 receptor antagonist; Drug: Neurokinin-1 receptor antagonist; Drug: Corticosteroid

Docetetaxel

ACTIVE COMPARATOR

Participants receive docetaxel 75mg/m2 via IV infusion q3w until disease progression or discontinuation criterion is met.

Drug: Docetetaxel; Drug: Corticosteroid

Interventions

Ifinatamab Deruxtecan BIOLOGICAL

IV Infusion

Also known as: I-DXd, MK-2400, DS-7300a

Ifinatamab Deruxtecan

Docetetaxel DRUG

IV Infusion

Docetetaxel

Corticosteroid DRUG

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

Docetetaxel; Ifinatamab Deruxtecan; Raludotatug Deruxtecan

Raludotatug Deruxtecan BIOLOGICAL

IV Infusion

Also known as: R-DXd, MK-5909, DS-6000a

Raludotatug Deruxtecan

5-hydroxytryptamine subtype 3 receptor antagonist DRUG

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

Also known as: 5-HT3 receptor antagonist

Ifinatamab Deruxtecan; Raludotatug Deruxtecan

Neurokinin-1 receptor antagonist DRUG

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

Also known as: NK-1 receptor antagonist

Ifinatamab Deruxtecan; Raludotatug Deruxtecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Daiichi Sankyo: collaborator
• Merck Sharp & Dohme LLC: lead

Study Sites (32)

University of Kentucky Chandler Medical Center ( Site 0019)

Lexington, Kentucky, 40536-0293, United States

RECRUITING

MedStar Franklin Square Medical Center ( Site 0033)

Baltimore, Maryland, 21237, United States

RECRUITING

Texas Oncology - DFW ( Site 8003)

Dallas, Texas, 75246-2046, United States

RECRUITING

Centro de Estudios Clínicos SAGA ( Site 0161)

Santiago, Region M. de Santiago, 7500653, Chile

RECRUITING

FALP ( Site 0160)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Bradfordhill ( Site 0162)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

Universitaetsklinik Tuebingen ( Site 0192)

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Charite-Universitaetsmedizin Berlin ( Site 0191)

Berlin, 13353, Germany

RECRUITING

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

Athens, Attica, 115 27, Greece

RECRUITING

European Interbalkan Medical Center ( Site 0205)

Thessaloniki, 570 01, Greece

RECRUITING

Bacs-Kiskun Varmegyei Oktatokorhaz ( Site 0063)

Kecskemét, Bács-Kiskun county, 6000, Hungary

RECRUITING

Petz Aladar Egyetemi Oktato Korhaz ( Site 0062)

Győr, Győr-Moson-Sopron, 9024, Hungary

RECRUITING

Jasz-Nagykun-Szolnok Megyei Hetenyi Gyula Korhaz-Rendelointezet ( Site 0061)

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

RECRUITING

Rambam Health Care Campus ( Site 0076)

Haifa, 3109601, Israel

RECRUITING

Shaare Zedek Medical Center ( Site 0075)

Jerusalem, 9103102, Israel

RECRUITING

Meir Medical Center ( Site 0071)

Kfar Saba, 4428164, Israel

RECRUITING

Rabin Medical Center ( Site 0074)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical Center ( Site 0070)

Ramat Gan, 5265601, Israel

RECRUITING

Sourasky Medical Center ( Site 0077)

Tel Aviv, 6423906, Israel

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175)

Milan, Lombardy, 20133, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi ( Site 0173)

Florence, 50134, Italy

RECRUITING

Ospedale San Raffaele. ( Site 0171)

Milan, 20132, Italy

RECRUITING

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

Roma, 00168, Italy

RECRUITING

Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0153)

Poznan, Greater Poland Voivodeship, 60-569, Poland

RECRUITING

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

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

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

Gdansk, Pomeranian Voivodeship, 80-214, Poland

RECRUITING

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

Koszalin, West Pomeranian Voivodeship, 75-581, Poland

RECRUITING

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

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital Universitario Quiron Madrid ( Site 0091)

Madrid, 28223, Spain

RECRUITING

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

Adana, 01250, Turkey (Türkiye)

RECRUITING

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0140)

Ankara, 06230, Turkey (Türkiye)

RECRUITING

I. U. Cerrahpasa Tip Fakultesi ( Site 0144)

Istanbul, 34098, Turkey (Türkiye)

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

Serotonin 5-HT3 Receptor Antagonists; Neurokinin-1 Receptor Antagonists; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Unblinded open-label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: January 17, 2025
• Study Start: May 13, 2025
• Primary Completion (Estimated): March 12, 2032
• Study Completion (Estimated): March 12, 2032
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

GR (2); PL (4); IT (4); CL (3); IL (6); ES (2); DE (2); HU (3); TU (3); US (3)