A Study of Pembrolizumab With or Without Chemotherapy in Combination With Additional Treatments for Advanced Non-Small Cell Lung Cancer (NSCLC) (MK-3475-01G/KEYMAKER U01)

Official title

KEYMAKER-U01 Substudy 01G: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents in Combination With Pembrolizumab With or Without Platinum-based Chemotherapy in Treatment-Naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)

Overview

Researchers are investigating new treatments for untreated advanced non-small cell lung cancer (NSCLC), which is the most common form of lung cancer and lung cancer that has spread beyond surgical removal. Standard treatments include immunotherapy, such as pembrolizumab, and chemotherapy. This study aims to determine the effectiveness of adding other treatments, including the human epidermal growth factor receptor 3-directed antibody-drug conjugate (HER3-DXd) patritumab deruxtecan, to pembrolizumab, with or without chemotherapy. The primary goals are to assess safety and efficacy of the treatments.

Interventions

• Biological Pembrolizumab
  Pembrolizumab 200mg IV Infusion.
• Drug Carboplatin
  Carboplatin IV infusion AUC5 or 6 mg/mL•min and not exceeding 900mg.
• Drug Paclitaxel
  Paclitaxel 200 mg/m\^2 IV infusion.
• Drug Nab-paclitaxel
  Nab-paclitaxel 100mg/m\^2 IV infusion.
• Drug Pemetrexed
  Pemetrexed 500mg/m\^2 IV infusion.
• Biological HER3-DXd
  HER3-Dxd 5.6mg/kg IV infusion.

Primary outcome measures

• Overall Response Rate (ORR) [Time frame: Up to ~ 5 years]
• Number of Participants with Adverse Events (AEs) [Time frame: Up to ~ 5 years]
• Number of Participants Discontinuing Study Drug Due to AEs [Time frame: Up to ~ 2 years]

Secondary outcome measures (3)

• Duration of Response (DOR) [Time frame: Up to ~ 5 years]
• Progression-free Survival (PFS) [Time frame: Up to ~ 5 years]
• Overall Survival (OS) [Time frame: Up to ~ 5 years]

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 or non-squamous non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) Staging Manual Version 8.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 7 days before randomization.
• Has archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided.
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on 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 prior to treatment randomization.

Exclusion criteria

The main exclusion criteria include but are not limited to the following:

• Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
• Participants with squamous histology are excluded if there is a known tumor-activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) or c ros oncogene 1 (ROS1) gene rearrangement.
• Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement.
• Has evidence of any leptomeningeal disease.
• Has known history of, or active, neurologic paraneoplastic syndrome.
• Has clinically significant corneal disease.
• Has myocardial infarction within 6 months.
• Has New York Heart Association (NYHA) Classes 3 or 4 congestive heart failure.
• Has uncontrolled angina pectoris within 6 months.
• Has cardiac arrhythmia requiring ongoing antiarrhythmic treatment.
• Has history of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
• Has bradycardia of less than 50 beats per minute (bpm) unless the participant has a pacemaker.
• Has history of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
• Has coronary/peripheral artery bypass graft within 6 months.
• Has complete left bundle branch block.
• Has inadequate washout period from prior concomitant therapy as specified in protocol before randomization.
• Has received prior treatment with a topoisomerase I inhibitor or an anti-HER3 antibody and/or ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor.
• Has received prior systemic anticancer therapy for their metastatic NSCLC.
• Has received prior therapy with an anti- programmed cell death 1 protein (anti-PD-1), anti- programmed cell death ligand 1 protein (anti-PD-L1), or anti- programmed cell death ligand 2 protein (anti-PD-L2) agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
• Has received prior radiotherapy within 2 weeks of randomization, has radiation related toxicity requiring corticosteroids, or has had radiation pneumonitis.
• Has received radiation therapy to the lung that is >30 gray within 6 months of start of study intervention.
• 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 or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
• Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity to any of the study interventions and/or any of their excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Has active infection requiring systemic therapy.
• Has concurrent active Hepatitis B and Hepatitis C virus infection.
• 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

Ukraine · 6 centers

• CNE CC of Oncology Hematol ( Site 0130) — Cherkasy
• Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 0136) — Chernivtsi
• CNCE Precarpathian Clinical Oncologic Center ( Site 0131) — Ivano-Frankivsk
• VISION PARTNER Medical Centre ( Site 0134) — Kyiv
• Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional — Vinnytsia
• Shalimov Institute of Surgery and Transplantation ( Site 0135) — Kyiv

United States · 5 centers

• University of Kentucky ( Site 0019) — Lexington
• MedStar Franklin Square Medical Center ( Site 0033) — Baltimore
• Sanford Fargo Medical Center ( Site 0039) — Fargo
• Abramson Cancer Center ( Site 0010) — Philadelphia
• Sanford Cancer Center ( Site 0038) — Sioux Falls

Poland · 4 centers

• Wielkopolskie Centrum Pulmonologii i Torakochirurgii-Oddzial Onkologii Klinicznej z Pododd — 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-Oddzial Dzienny Chemioterapii ( Site — Koszalin

Chile · 3 centers

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

Hungary · 3 centers

• Petz Aladar Egyetemi Oktato Korhaz ( Site 0062) — Győr
• Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet ( Site 0061) — Szolnok
• Országos Korányi Pulmonológiai Intézet ( Site 0060) — Budapest

Italy · 3 centers

• Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175) — Milan
• IRCCS Ospedale San Raffaele ( Site 0171) — Milan
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sac — Roma

Spain · 3 centers

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

Taiwan · 3 centers

• Changhua Christian Hospital ( Site 0181) — Changhua
• Taipei Medical University Hospital ( Site 0180) — Taipei
• Chang Gung Medical Foundation-Linkou Branch ( Site 0182) — Taoyuan

Turkey (Türkiye) · 3 centers

• Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0141) — Adana
• Hacettepe Universite Hastaneleri ( Site 0140) — Ankara
• Ankara Bilkent Şehir Hastanesi ( Site 0142) — Ankara

Greece · 2 centers

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

Identifiers

NCT: NCT06731907 · 3475-01G · 2024-515772-12-00 · U1111-1309-7532 · KEYMAKER U01 · MK-3475-01G

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗