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)

New lung cancer drug study seeks patients who previously failed standard treatment

NCT: NCT06780098 · Status: RECRUITING · Phase: Phase 2 · Sponsor: Merck Sharp & Dohme LLC · Started: 2025-05-28 · Est. Completion: 2032-03-02

Plain English Summary

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) is a Phase 2 clinical trial sponsored by Merck Sharp & Dohme LLC studying Lung Neoplasm. This study tests new investigational drugs, called antibody drug conjugates (ADCs), to see if they can treat advanced squamous non-small cell lung cancer (NSCLC) that has not responded to standard treatments. It is for adults with Stage IV squamous NSCLC that has spread and has not improved after prior immunotherapy and chemotherapy. Participants will be randomly assigned to receive one of the study drugs or standard chemotherapy, and will receive rescue medications to manage side effects. Alternative treatments may include continuing standard chemotherapy, other clinical trials, or palliative care. The trial aims to enroll 144 participants.

Official 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).

Who Can Participate

Here is what you need to know about eligibility for this trial. You may be eligible if you have been diagnosed with Stage IV squamous non-small cell lung cancer that has spread and has not responded to previous immunotherapy and chemotherapy. You cannot join if you have small cell lung cancer, untreated brain metastases, active autoimmune disease requiring systemic treatment, or certain other serious health conditions. Participants must be at least 18 years old and have controlled HIV, Hepatitis B, or Hepatitis C if applicable. Any side effects from previous cancer treatments must have mostly resolved before you can join. This trial is studying Lung Neoplasm, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures, such as how many patients' tumors shrink or disappear (Objective Response Rate), will show how effective the study drugs are at fighting the cancer. The specific primary outcome measures are: Objective Response Rate (ORR) (Up to approximately 81 months); Number of participants who experience one or more adverse events (AEs) (Up to approximately 81 months); Number of participants who discontinue study intervention due to an AE (Up to approximately 81 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for new treatments for patients with advanced squamous NSCLC whose cancer has progressed after standard therapies, offering a potential new option when current tre Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Lung Neoplasm, where improved treatment options are needed.

Investor Insight

This trial, sponsored by Merck, explores novel antibody drug conjugates in a significant market of previously treated NSCLC patients, indicating a potential competitive advancement in targeted cancer Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific investigational drugs being tested, their potential benefits, and known side effects. Understand how you will be assigned to a treatment group and what the treatment schedule will involve. Discuss how your health will be monitored throughout the study and what support is available for managing side effects. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

Interventions

Primary Outcomes

Secondary Outcomes

Full Eligibility Criteria

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
* 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
* History of allogeneic tissue/solid organ transplant
* Has not adequately recovered from major surgery or have ongoing surgical complications

Trial Locations

Frequently Asked Questions

What is clinical trial NCT06780098?

NCT06780098 is a Phase 2 INTERVENTIONAL study titled "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)." It is currently recruiting and is sponsored by Merck Sharp & Dohme LLC. The trial targets enrollment of 144 participants.

What conditions does NCT06780098 study?

This trial investigates treatments for Lung Neoplasm. The primary condition under study is Lung Neoplasm.

What treatments are being tested in NCT06780098?

The interventions being studied include: R-DXD (BIOLOGICAL), I-DXD (BIOLOGICAL), Docetaxel (DRUG), Rescue Medications (DRUG), Rescue Medication (DRUG). IV Infusion

What does Phase 2 mean for NCT06780098?

Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.

What is the current status of NCT06780098?

This trial is currently "Recruiting." It started on 2025-05-28. The estimated completion date is 2032-03-02.

Who is sponsoring NCT06780098?

NCT06780098 is sponsored by Merck Sharp & Dohme LLC. The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT06780098?

The trial aims to enroll 144 participants. The trial is currently recruiting and accepting new participants.

How is NCT06780098 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs single masking. Masking means some participants and/or investigators do not know which treatment group a participant is in, which helps reduce bias.

What are the primary outcomes being measured in NCT06780098?

The primary outcome measures are: Objective Response Rate (ORR) (Up to approximately 81 months); Number of participants who experience one or more adverse events (AEs) (Up to approximately 81 months); Number of participants who discontinue study intervention due to an AE (Up to approximately 81 months). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT06780098 being conducted?

This trial is being conducted at 20 sites, including Lexington, Kentucky; Baltimore, Maryland; Santiago, Region M. de Santiago; Chongqing, Chongqing Municipality and 16 more sites (United States, Chile, China).

Where can I find official information about NCT06780098?

The official record for NCT06780098 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06780098. This government database provides the most up-to-date and detailed information about the trial.

What is NCT06780098 testing in simple terms?

This study tests new investigational drugs, called antibody drug conjugates (ADCs), to see if they can treat advanced squamous non-small cell lung cancer (NSCLC) that has not responded to standard treatments. It is for adults with Stage IV squamous NSCLC that has spread and has not improved after prior immunotherapy and chemotherapy.

Why is this trial significant?

This trial addresses a critical need for new treatments for patients with advanced squamous NSCLC whose cancer has progressed after standard therapies, offering a potential new option when current tre

What are the potential risks of participating in NCT06780098?

Common side effects may include fatigue, nausea, hair loss, and changes in blood counts. More serious risks can include severe allergic reactions, lung inflammation, or heart problems. Some participants may experience side effects that require stopping the study treatment. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT06780098?

Ask your doctor about the specific investigational drugs being tested, their potential benefits, and known side effects. Understand how you will be assigned to a treatment group and what the treatment schedule will involve. Discuss how your health will be monitored throughout the study and what support is available for managing side effects. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT06780098 signal from an investment perspective?

This trial, sponsored by Merck, explores novel antibody drug conjugates in a significant market of previously treated NSCLC patients, indicating a potential competitive advancement in targeted cancer This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.

What happens if the treatment in this trial doesn't work?

Participants will be randomly assigned to receive one of the study drugs or standard chemotherapy, and will receive rescue medications to manage side effects. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.