Recruiting
Phase 2

Antibody Drug Conjugates

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT06780085

Conditions

Carcinoma, Non-Small-Cell Lung

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Raludotatug Deruxtecan

Ifinatamab Deruxtecan

Docetetaxel

5-hydroxytryptamine subtype 3 receptor antagonist

Neurokinin-1 receptor antagonist

Study Details

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

Study ID

NCT06780085

Start date

May 13, 2025

Status verified date

Aug, 2026

Completion date

Mar 12, 2032

Anticipated

Primary completion date

Mar 12, 2032

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
  • 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

Exclusion Criteria:

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
  • 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

Study Design

Enrollment

96 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Raludotatug Deruxtecan

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.

experimental: Ifinatamab Deruxtecan

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

active comparator: Docetetaxel

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

Interventions

Raludotatug Deruxtecan

IV Infusion

Ifinatamab Deruxtecan

IV Infusion

Docetetaxel

IV Infusion

5-hydroxytryptamine subtype 3 receptor antagonist

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

Neurokinin-1 receptor antagonist

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

Corticosteroid

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

Primary outcome measure

  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 81 months ]
  • Percentage of Participants with at Least One Adverse Event (AE) [ Time Frame: Up to approximately 81 months ]
  • Percentage of Participants Who Discontinued Medication Due to an AE [ Time Frame: Up to approximately 24 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

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

Locations

University of Kentucky Chandler Medical Center ( Site 0019)

Recruiting

Lexington, Kentucky, United States, 40536-0293

Contacts

Study Coordinator

859-257-1000

MedStar Franklin Square Medical Center ( Site 0033)

Recruiting

Baltimore, Maryland, United States, 21237

Contacts

Study Coordinator

443-777-7147

AHN Cancer Institute - Allegheny General ( Site 9501)

Recruiting

Pittsburgh, Pennsylvania, United States, 15212

Contacts

Study Coordinator

412-325-5700

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Aug 25, 2026

Last verified

Aug, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-08-25.