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)

Merck Sharp & Dohme (MSD)

Status and phase

Enrolling

Phase 2

Conditions

Lung Neoplasm

Treatments

Biological: R-DXD

Drug: Docetaxel

Biological: I-DXD

Study type

Interventional

Funder types

Industry

Identifiers

NCT06780098

KEYMAKER-01I (Other Identifier)

U1111-1314-2392 (Other Identifier)

3475-01I

2024-518839-11-00 (Registry Identifier)

MK-3475-01I (Other Identifier)

Details and patient eligibility

About

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).

Full description

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

Enrollment

144 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

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
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
Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection (including HIV infection)
Has clinically significant corneal disease
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
History of (noninfectious) pneumonitis/Interstitial Lung Disease (ILD) that required steroids or has current pneumonitis/ILD, and/or suspected ILD/pneumonitis
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 design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

144 participants in 4 patient groups

Arm 1: Raludotatug deruxtecan (R-DXD)

Experimental group

Description:

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.

Treatment:

Biological: R-DXD

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

Experimental group

Description:

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

Treatment:

Biological: I-DXD

Arm 3: I-DXD Low Dose

Experimental group

Description:

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