RecruitingPhase 2

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)

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)

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests drugs that attach to cancer cells and deliver medicine to kill them. It is for people with stage IV squamous non-small cell lung cancer that has spread and grown after standard treatment. Researchers will compare how well the study drugs work with chemotherapy and check their safety.

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).

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have stage IV squamous non-small cell lung cancer confirmed by a tissue or cell test.
  • Have cancer that grew after both PD-1 or PD-L1 immunotherapy, which helps the immune system fight cancer, and platinum-based chemotherapy for stage IV cancer.
  • If you have HIV, it must be well controlled with HIV medicines.
  • If you test positive for hepatitis B surface antigen, you must have taken hepatitis B medicine for at least 4 weeks, with no virus detected in your blood.
  • If you have had hepatitis C, no hepatitis C virus can be detected in your blood.

Who can't join

  • Have small cell lung cancer, including a tumor with both small cell and other cancer cells.
  • Have serious or uncontrolled heart or blood vessel disease, serious breathing problems from other illnesses, or a past surgery to remove an entire lung.
  • Have current, suspected, or past lung scarring or inflammation called ILD or pneumonitis. Past radiation-related pneumonitis is allowed if it did not need steroids.
  • Have serious disease of the clear front of the eye; have previously received docetaxel; or still have more than mild side effects from past cancer treatment, unless back to your usual level. Hair loss is allowed.
  • Have another cancer that is growing or needed treatment in the past 3 years; untreated cancer spread to the brain or spinal cord; or cancer in their lining.
  • Have an immune system disease needing whole-body treatment in the past 2 years, an infection needing whole-body treatment, or current or past inflammatory bowel disease. Hormone replacement treatment is allowed. People with HIV cannot have a history of Kaposi's sarcoma or Multicentric Castleman's disease.
  • Have a current or past cancer-related nerve or brain condition called neurologic paraneoplastic syndrome, or have received tissue or an organ from a donor.
  • Have not healed enough after major surgery or still have problems from surgery.

Simplified for readability. The official criteria below are what the study team uses.

Official 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

Study sites (4)

KY

MD

TX

VA