RecruitingPhase 2

A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01)

KEYMAKER-U01 Substudy 01H: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous 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 compares two study drugs with chemotherapy for adults with stage IV nonsquamous non-small cell lung cancer that has spread and worsened after treatment. The study drugs attach to targets on cancer cells and deliver medicine to kill them. Researchers will check their safety and how well they shrink the cancer.

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

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

Eligibility

Who can join

  • You are at least 18 and have stage IV nonsquamous non-small cell lung cancer confirmed by a tissue or cell test.
  • Your cancer worsened after PD-1 or PD-L1 treatment, which helps the immune system fight cancer, and platinum-based chemotherapy.
  • Tumor tests show that treatments aimed at certain gene changes, such as EGFR, ALK, or ROS1, are not suitable as your main treatment.
  • Your cancer can be measured on scans. You can do most daily activities, your organs work well enough, and you are expected to live at least 3 months.
  • You must provide stored tumor tissue from an area not treated with radiation and a new tissue sample taken before treatment assignment.
  • If you can become pregnant, you must have a negative pregnancy test, not breastfeed, and use highly effective birth control. If you can produce sperm, you must not donate it and must avoid vaginal sex or use an external condom.
  • If you have HIV, it must be well controlled with HIV medicine.
  • If you have hepatitis B, you must have taken antiviral medicine for at least 4 weeks and have no virus detected before treatment assignment. If you have had hepatitis C, no virus can be detected at screening.

Who can't join

  • You have small cell lung cancer, even as part of a mixed tumor; untreated cancer spread to the brain or spinal cord; cancer in their lining; or another cancer that is growing or needed treatment in the past 3 years.
  • You have had radiation to the lungs, severe breathing problems, or past, current, or suspected lung inflammation called interstitial lung disease or pneumonitis.
  • You have a serious or uncontrolled heart or blood vessel problem, significant disease of the clear front of the eye, or a severe allergy to a study drug or its ingredients.
  • You have a weak immune system, take ongoing steroids that affect the whole body, have an autoimmune disease needing whole-body treatment in the past 2 years, or have an infection needing whole-body treatment.
  • You have current or past inflammatory bowel disease, a cancer-related nerve disorder, a tissue or organ transplant from another person, or HIV with a history of Kaposi’s sarcoma or Multicentric Castleman’s disease.
  • You have received docetaxel, used an experimental drug or device within 4 weeks, or received a live vaccine within 30 days before study treatment.
  • You had radiation within 2 weeks before study treatment, have radiation side effects needing steroids, or have not waited long enough after earlier treatment.
  • Side effects from past cancer treatment have not returned to mild levels or your usual health, except hair loss, or you have not recovered enough from major 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 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 sites (3)

KY

MD

PA