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

Official title

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)

Overview

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

Detailed description

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

Interventions

• Biological Raludotatug Deruxtecan
  IV Infusion
• Biological Ifinatamab Deruxtecan
  IV Infusion
• Drug Docetetaxel
  IV Infusion
• Drug 5-hydroxytryptamine subtype 3 receptor antagonist
  Administered as a rescue medication per approved product label before R-DXd or I-DXd infusion
• Drug Neurokinin-1 receptor antagonist
  Administered as a rescue medication per approved product label before R-DXd or I-DXd infusion
• Drug 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 measures

• 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]

Secondary outcome measures (3)

• Duration of Response (DOR) [Time frame: Up to approximately 81 months]
• Progression-free Survival (PFS) [Time frame: Up to approximately 81 months]
• Overall Survival (OS) [Time frame: Up to approximately 81 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Israel · 6 centers

• Rambam Health Care Campus ( Site 0076) — Haifa
• Shaare Zedek Medical Center ( Site 0075) — Jerusalem
• Meir Medical Center ( Site 0071) — Kfar Saba
• Rabin Medical Center ( Site 0074) — Petah Tikva
• Sheba Medical Center ( Site 0070) — Ramat Gan
• Sourasky Medical Center ( Site 0077) — Tel Aviv

Turkey (Türkiye) · 5 centers

• Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 0141) — Adana
• Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0140) — Ankara
• Ankara Bilkent Şehir Hastanesi. ( Site 0142) — Ankara
• I. U. Cerrahpasa Tip Fakultesi ( Site 0144) — Istanbul
• Ege Universitesi Hastanesi ( Site 0143) — Izmir

Italy · 4 centers

• Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175) — Milan
• Azienda Ospedaliera Universitaria Careggi ( Site 0173) — Florence
• Ospedale San Raffaele. ( Site 0171) — Milan
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sac — Roma

Poland · 4 centers

• Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0153) — Poznan
• Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w W — Warsaw
• Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150) — Gdansk
• Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie ( Site 0152) — Koszalin

United States · 3 centers

• University of Kentucky Chandler Medical Center ( Site 0019) — Lexington
• MedStar Franklin Square Medical Center ( Site 0033) — Baltimore
• AHN Cancer Institute - Allegheny General ( Site 9501) — Pittsburgh

Chile · 3 centers

• Centro de Estudios Clínicos SAGA ( Site 0161) — Santiago
• FALP ( Site 0160) — Santiago
• Bradfordhill ( Site 0162) — Santiago

Hungary · 3 centers

• Bacs-Kiskun Varmegyei Oktatokorhaz ( Site 0063) — Kecskemét
• Petz Aladar Egyetemi Oktato Korhaz ( Site 0062) — Győr
• Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet ( Site 0061) — Szolnok

Germany · 2 centers

• Universitaetsklinik Tuebingen ( Site 0192) — Tübingen
• Charite-Universitaetsmedizin Berlin ( Site 0191) — Berlin

Greece · 2 centers

• THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA"-3rd Dept of Internal Medicine and Laborato — Athens
• European Interbalkan Medical Center ( Site 0205) — Thessaloniki

Spain · 2 centers

• Institut Català d'Oncologia - L'Hospitalet ( Site 0090) — L'Hospitalet de Llobregat
• Hospital Universitario Quiron Madrid ( Site 0091) — Madrid

Identifiers

NCT: NCT06780085 · 3475-01H · 2024-518761-10-00 · MK-3475-01H · U1111-1314-1785 · KEYMAKER-U01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗