A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer

Официальное название

A Phase 2, Open-Label, Parallel Cohort Study of Subcutaneous Amivantamab in Multiple Regimens in Patients With Advanced or Metastatic Solid Tumors Including EGFR-mutated Non-Small Cell Lung Cancer

Обзор

The purpose of this study is to assess the anti-tumor activity and safety of amivantamab which will be administered as a co-formulation with recombinant human hyaluronidase PH20 (rHuPH20) (subcutaneous co-formulation \[SC-CF\]) in combination treatment (all cohorts except Cohort 4) and to characterize the safety of amivantamab SC-CF (Cohort 4).

Вмешательства

• Препарат Amivantamab
  Amivantamab will be administered subcutaneously by manual injection.
• Препарат Lazertinib
  Lazertinib will be administered as an oral tablet.
• Препарат Carboplatin
  Carboplatin will be administrated by IV infusion.
• Препарат Pemetrexed
  Pemetrexed will be administered by IV infusion.
• Препарат Direct Oral Anticoagulant (DOAC)
  DOAC will be administered orally.
• Препарат Low Molecular Weight Heparin (LMWH)
  LMWH will be administered subcutaneously.

Первичные конечные точки

• All Cohorts Except Cohort 4: Objective Response Rate (ORR) Based on Investigator Assessment (INV) [Срок оценки: Up to 1 year 6 months]
• Cohort 4: Number of Participants with Adverse Events (AEs) [Срок оценки: Up to approximately 4 years and 9 months]
• Cohort 4: Number of Participants with AEs by Severity [Срок оценки: Up to approximately 4 years and 9 months]
• Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values [Срок оценки: Up to approximately 4 years and 9 months]
• Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity [Срок оценки: Up to approximately 4 years and 9 months]

Вторичные конечные точки (12)

• All Cohorts Except Cohort 4: Number of Participants with AEs [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: Number of Participants with AEs by Severity [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: ORR Based on Independent Central Review (ICR) [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: Duration of Response (DoR) Based on Investigator Assessment (INV) [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: Time to Response (TTR) Based on INV [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: Clinical Benefit Rate (CBR) [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: Progression-free Survival (PFS) [Срок оценки: Up to 3 years]
• All Cohorts Except Cohort 4: Overall Survival (OS) [Срок оценки: Up to approximately 4 years]
• All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE) [Срок оценки: Up to 1 year 6 months]
• All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE) by Severity [Срок оценки: Up to 1 year 6 months]

Критерии участия

Критерии включения

• Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-small cell lung cancer (NSCLC) that is not amenable to curative therapy including surgical resection or chemoradiation. Additional Cohort specific disease requirements include: Cohorts 1, 3, 3b, 5, 6 and 7: epidermal growth factor receptor (EGFR) exon 19 deletion (Exon19del) or Exon 21 L858R mutation; Cohort 2: EGFR Exon 20ins mutation. Cohorts 1,5,and6: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohort 2: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohorts 3and3b: Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second-line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Cohort 4: Participants need to currently be on an amivantamab IV Q2W regimen (1,050 mg or 1,400 mg depending on weight) for at least 8 weeks, as part of standard of care, an expanded access program, or as a rollover from a long-term extension, without any amivantamab dose reduction. Cohort 7: Participants must have progressed on or after the combination of amivantamab and lazertinib as the most recent line of treatment. The combination of amivantamab and lazertinib must have been administered as the first-line treatment for locally advanced or metastatic disease. Cohort 2, 3, 3b, and 7 only: Squamous NSCLC are excluded. EGFR mutation must have been identified as determined by Food and Drug Administration (FDA) approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United states \[US\]) or an accredited local laboratory (sites outside of the US). A copy of the initial test report documenting the EGFR mutation must be included in the participant records and a deidentified copy must also be submitted to the sponsor
• All cohorts except Cohort 4: Participants must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed If only 1 non-irradiated measurable lesion exists, which undergoes a biopsy and is acceptable as a target lesion, the baseline tumor assessment scans should be performed at least 14 days after the biopsy
• May have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
• Have adequate organ (renal, hepatic, hematological, coagulation and cardiac) functions
• Participant must have eastern cooperative oncology group (ECOG) status of 0 or 1
• Cohort 6: Must be eligible for, and agree to comply with, the use of prophylactic anticoagulation with a direct oral anticoagulant or a low molecular weight heparin during the first 4 months of study treatment
• A participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Participants with child bearing potential should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility

Критерии исключения

• Participant has a medical history of interstitial lung disease (ILD), including drug induced ILD or radiation pneumonitis
• Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrollment cohort
• Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against Coronavirus disease 19 (COVID-19) are not exclusionary
• For all cohorts (with regimens potentially including lazertinib): Participant is currently receiving medications or herbal supplements known to be potent Cytochrome (CYP3A4/5) inducers and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1
• Other clinically active liver disease of infectious origin
• Participant has a history of clinically significant cardiovascular disease including, but not limited to: a) All cohorts: diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment(s), or any of the following within 6 months prior to the first dose of study treatment(s): myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary; b) All cohorts (with regimens potentially including lazertinib): Participant has a significant genetic predisposition to venous thromboembolic events (VTE; such as Factor V Leiden); c) All cohorts (with regimens potentially including lazertinib): Participant has a prior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines; d) prolonged corrected QT interval by Fridericia (QTcF) interval greater than (>) 480 milliseconds (msec) or clinically significant cardiac arrhythmia or electrophysiologic disease (example, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate); e) uncontrolled (persistent) hypertension: systolic blood pressure >160 millimeter(s) of mercury (mmHg); diastolic blood pressure >100 mmHg; f) Congestive heart failure defined as NYHA class III-IV or hospitalization for congestive heart failure (CHF) (any New York Heart Association \[NYHA\] class) within 6 months of treatment initiation at Cycle 1/day 1 (C1D1); g) pericarditis/clinically significant pericardial effusion; h) myocarditis; i) baseline left ventricular ejection fraction (LVEF) below the institution's lower limit of normal at screening, as assessed by echocardiogram or multigated acquisition (MUGA) scan
• Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (less than or equal to \[<=\] 10 milligrams per day \[mg/day\] prednisone or equivalent) for at least 2 weeks prior to treatment allocation

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 26 центров

• University of California at San Diego — La Jolla
• University of California Irvine — Orange
• Stanford Cancer Institute — Stanford
• Johns Hopkins Office of Capital Region Research - Sibley Memorial Hospital — Washington D.C.
• Baptist Lynn Cancer Institute — Boca Raton
• Mount Sinai Medical Center — Miami Beach
• AdventHealth — Orlando
• H. Lee Moffitt Cancer & Research Institute — Tampa
• … и ещё 18 центров

Китай · 18 центров

• Affiliated Hospital of Hebei University — Baoding
• Jilin cancer hospital — Changchun
• Sichuan Cancer Hospital — Чэнду
• West China Hospital Sichuan University — Чэнду
• The First Affiliated Hospital of PLA Army Medical University — Чунцин
• The First Affiliated Hospital Sun Yat sen University — Гуанчжоу
• The First Affiliated Hospital Zhejiang University College of Medicine — Ханчжоу
• Sir Run Run Shaw Hospital Zhejiang University School of Medicine — Ханчжоу
• … и ещё 10 центров

Испания · 14 центров

Список центров уточняется — проверьте первичный протокол.

Бразилия · 9 центров

• Fundacao Pio XII — Barretos
• PERSONAL Oncologia de Precisao e Personalizada — Belo Horizonte
• Instituto do Cancer de Londrina Hospital do Cancer de Londrina — Londrina
• Associacao Hospitalar Moinhos de Vento — Porto Alegre
• Instituto D Or de Pesquisa e Ensino IDOR — Rio de Janeiro
• Instituto D Or de Pesquisa e Ensino IDOR 1 — Salvador
• Hospital Alemao Oswaldo Cruz — São Paulo
• Impar Servicos Hospitalares SA Hospital Nove de Julho — São Paulo
• … и ещё 1 центр

Великобритания · 7 центров

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Франция · 6 центров

• Centre Francois Baclesse — Caen
• Centre Georges-François Leclerc — Dijon
• Institut de Cancérologie du Gard — Nîmes
• Institut Curie — Paris
• Institut de cancerologie de l'ouest — Saint-Herblain
• Gustave Roussy — Villejuif

Япония · 6 центров

• National Hospital Organization Himeji Medical Center — Himeji
• Saiseikai Matsusaka Municipal Hospital — Matsusaka
• Niigata Cancer Center Hospital — Niigata
• Shizuoka Cancer Center — Shizuoka
• The Cancer Institute Hospital of JFCR — Tokyo
• Wakayama Medical University Hospital — Wakayama

Германия · 5 центров

• Evangelische Lungenklinik Berlin — Berlin
• Universitaetsklinikum Koeln — Cologne
• LungenClinic Grosshansdorf GmbH — Grosshandorf
• Lungenfachklinik Immenhausen — Immenhausen
• Klinikum Würzburg Mitte gGmbH Standort Missioklinik — Würzburg

Израиль · 5 центров

• Rambam Medical Center — Haifa
• Shaare Zedek Medical Center — Jerusalem
• Meir Medical Center — Kfar Saba
• Rabin Medical Center — Petah Tikva
• Sheba Medical Center — Ramat Gan

Италия · 5 центров

• Policlinico Hospital San Martino- IRCCS for Oncology — Genova
• Ospedale San Raffaele — Milan
• ASST Grande Ospedale Metropolitano Niguarda — Milan
• Azienda Ospedaliera San Gerardo — Monza
• Azienda Ospedaliera Specialistica dei Colli — Naples

South Korea · 5 центров

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Малайзия · 4 центра

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Идентификаторы

NCT: NCT05498428 · CR109264 · 61186372NSC2002 · 2022-000526-21 · 2023-505065-91-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗