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


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
Joel Neal, MD, PhD

Associate Professor of Medicine (Oncology)


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


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

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