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A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer
Not Recruiting
Trial ID: NCT05498428
Purpose
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).
Official Title
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
Stanford Investigator(s)
Joel Neal, MD, PhD
Associate Professor of Medicine (Oncology)
Eligibility
Inclusion Criteria:
- 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. Female participants should
consider preservation of eggs prior to study treatment as anti-cancer treatments may
impair fertility
Exclusion Criteria:
- 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
Intervention(s):
drug: Amivantamab
drug: Lazertinib
drug: Carboplatin
drug: Pemetrexed
drug: Direct Oral Anticoagulant (DOAC)
drug: Low Molecular Weight Heparin (LMWH)
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
Richard A Quick
650-723-2983