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)

Official title

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)

Overview

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).

Detailed description

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

Interventions

• Biological R-DXD
  IV Infusion
• Biological I-DXD
  IV Infusion
• Drug Docetaxel
  IV Infusion
• Drug Rescue Medications
  Participants receive rescue medications consisting of a combination regimen to include corticosteroids with a 5-hydroxytryptamine subtype 3 receptor antagonist and/or a neurokinin-1 receptor antagonist, all per approved product label and following institutional standards or local guidelines.
• Drug Rescue Medication
  Participants are premedicated with corticosteroids per approved product label and following institutional standards or local guidelines.

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: Up to approximately 81 months]
• Number of participants who experience one or more adverse events (AEs) [Time frame: Up to approximately 81 months]
• Number of participants who discontinue study intervention due to an AE [Time frame: Up to approximately 81 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 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

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

China · 8 centers

• Beijing Cancer Hospital ( Site 0301) — Beijing
• Chongqing University Cancer Hospital ( Site 0304) — Chongqing
• Fujian Provincial Cancer Hospital ( Site 0310) — Fuzhou
• Guangxi Medical University Cancer Hospital ( Site 0303) — Nanning
• Henan Cancer Hospital ( Site 0311) — Zhengzhou
• Nanjing Drum Tower Hospital JiangBei International Branch Hospital ( Site 0309) — Nanjing
• Shanghai Chest Hospital ( Site 0308) — Shanghai
• Shanghai Pulmonary Hospital ( Site 0300) — Shanghai

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

• Ege Universitesi Hastanesi ( Site 0143) — Izmir
• 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
• Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0144) — Istanbul

Italy · 4 centers

• Azienda Ospedaliera Universitaria Careggi ( Site 0173) — Florence
• Ospedale San Raffaele. ( Site 0171) — Milan
• Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175) — 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
• Texas Oncology - DFW ( Site 8003) — Dallas

Chile · 3 centers

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

Greece · 3 centers

• EVANGELISMOS S.A ( Site 0206) — Athens
• THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA" ( Site 0204) — Athens
• European Interbalkan Medical Center-Oncology Department ( Site 0205) — Thessaloniki

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

Spain · 3 centers

• Institut Català d'Oncologia - L'Hospitalet ( Site 0090) — L'Hospitalet de Llobregat
• Hospital Clinic de Barcelona ( Site 0092) — Barcelona
• Hospital Universitario Quiron Madrid ( Site 0091) — Madrid

Germany · 2 centers

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

Identifiers

NCT: NCT06780098 · 3475-01I · MK-3475-01I · U1111-1314-2392 · 2024-518839-11-00 · KEYMAKER-01I

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗