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)

NCT06780098 | Recruiting Phase 2 FDA Drug

• 5 other identifiers: 3475-01IMK-3475-01IU1111-1314-23922024-518839-11-00KEYMAKER-01I
• Study Type: interventional
• Target: 144
• Locations: 11 countries
• Sites: 40

Brief 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. 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. 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).

Conditions

Lung Neoplasm

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 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.

  Up to approximately 81 months

• 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.

  Up to approximately 81 months

• 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.

  Up to approximately 81 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 (4)

Arm 1: Raludotatug deruxtecan (R-DXD)

EXPERIMENTAL

Participants 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.

Biological: R-DXD; Drug: Rescue Medications

Arm 2: Infinatamab deruxtecan (I-DXD) High Dose

EXPERIMENTAL

Participants receive 12 mg/kg of I-DXD, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.

Biological: I-DXD; Drug: Rescue Medications

Arm 3: I-DXD Low Dose

EXPERIMENTAL

Participants receive 8 mg/kg of I-DXD, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.

Biological: I-DXD; Drug: Rescue Medications

Arm 4: Docetaxel

ACTIVE COMPARATOR

Participants receive 75 mg/m\^2 of Docetaxel, Q3W (Day 1 of every 21-day cycle) via IV infusion until PD or discontinuation.

Drug: Docetaxel; Drug: Rescue Medication

Interventions

R-DXD BIOLOGICAL

IV Infusion

Also known as: Raludotatug deruxtecan, MK-5909, DS-6000a

Arm 1: Raludotatug deruxtecan (R-DXD)

I-DXD BIOLOGICAL

IV Infusion

Also known as: Ifinatamab deruxtecan, MK-2400, DS-7300a

Arm 2: Infinatamab deruxtecan (I-DXD) High Dose; Arm 3: I-DXD Low Dose

Docetaxel DRUG

IV Infusion

Also known as: Taxotere®

Arm 4: Docetaxel

Rescue Medication DRUG

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

Arm 4: Docetaxel

Rescue Medications DRUG

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.

Arm 1: Raludotatug deruxtecan (R-DXD); Arm 2: Infinatamab deruxtecan (I-DXD) High Dose; Arm 3: I-DXD Low Dose

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 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

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

Study Sites (40)

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

Chongqing University Cancer Hospital ( Site 0304)

Chongqing, Chongqing Municipality, 400030, China

RECRUITING

Fujian Provincial Cancer Hospital ( Site 0310)

Fuzhou, Fujian, 350014, China

RECRUITING

Guangxi Medical University Cancer Hospital ( Site 0303)

Nanning, Guangxi, 530201, China

RECRUITING

Henan Cancer Hospital ( Site 0311)

Zhengzhou, Henan, 450000, China

RECRUITING

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

Nanjing, Jiangsu, 210031, China

RECRUITING

Shanghai Chest Hospital ( Site 0308)

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Shanghai Pulmonary Hospital ( Site 0300)

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

UniversitaetsklInikum 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" ( Site 0204)

Athens, Attica, 115 27, Greece

RECRUITING

European Interbalkan Medical Center-Oncology Department ( 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

Azienda Ospedaliera Universitaria Careggi ( Site 0173)

Florence, 50134, Italy

RECRUITING

Ospedale San Raffaele. ( Site 0171)

Milan, 20132, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175)

Milan, 20133, 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 Clinic de Barcelona ( Site 0092)

Barcelona, 08008, 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

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0144)

Istanbul, 34098, Turkey (Türkiye)

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Docetaxel

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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
• 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 28, 2025
• Primary Completion (Estimated): March 2, 2032
• Study Completion (Estimated): March 2, 2032
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

PL (4); IT (4); HU (3); CL (3); IL (6); GR (2); DE (2); US (3); TU (3); CN (7); ES (3)