RecruitingPhase 2

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests amivantamab mixed with rHuPH20 and given as a shot under the skin, usually with other cancer drugs. It checks safety and, in most groups, how well treatment fights cancer. It is for people with advanced non-small cell lung cancer that cannot be cured with surgery or combined chemotherapy and radiation.

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).

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have non-small cell lung cancer confirmed by a tissue or cell test. The cancer must have spread nearby or to other parts of the body. Most groups require specific changes in the EGFR gene, confirmed by an approved or validated test.
  • Prior treatment rules depend on the group: groups 1, 2, 5 and 6 allow no prior whole-body treatment for advanced lung cancer. Groups 3 and 3b require cancer that worsened after osimertinib given alone as the most recent treatment. Group 7 requires cancer that worsened after amivantamab plus lazertinib given as the first and most recent treatment.
  • Group 4: Have received amivantamab through a vein every 2 weeks for at least 8 weeks, at the required weight-based dose, without a dose reduction.
  • Except in group 4, have at least one tumor that can be measured. Special rules apply if that tumor was treated with radiation or had a biopsy.
  • Have organs that work well enough for treatment. Be fully active or able to do light work despite some limits on hard physical activity.
  • A second cancer may be allowed if it is unlikely to affect study safety or results.
  • Group 6: Be able and willing to take the required blood-thinning medicine to help prevent clots during the first 4 months.
  • Agree not to donate eggs or freeze eggs for future pregnancy during treatment and for 6 months after the last dose. Consider freezing eggs before treatment, since cancer drugs may affect the ability to have children.

Who can't join

  • Groups 2, 3, 3b and 7: Have the squamous cell type of non-small cell lung cancer.
  • Have a history of interstitial lung disease, which causes lung inflammation or scarring, including lung inflammation caused by drugs or radiation.
  • Have a history of an allergic reaction to added ingredients in the study drugs for your group.
  • Received a live or weakened-live vaccine within 3 months before starting treatment. Seasonal flu vaccines and non-live COVID-19 vaccines do not rule you out.
  • For groups that may use lazertinib: Take certain medicines or herbs that affect how drugs are broken down and cannot stop them long enough before treatment.
  • Have another active liver disease caused by an infection.
  • Have certain serious heart, blood vessel or blood-clot problems. These include a deep vein or lung clot within 1 month; certain heart attacks, strokes or artery bypass surgery within 6 months; serious heart rhythm or pumping problems; uncontrolled high blood pressure; or heart inflammation. Groups that may use lazertinib have extra rules about inherited clot risk and past clots.
  • Have cancer in the brain that causes symptoms. Brain cancer spread without symptoms, or previously treated and stable brain cancer spread, may be allowed. After treatment for symptoms or unstable brain disease, you must meet rules for at least 2 weeks of stability and no steroids or only a low dose.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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. Participants with child bearing potential 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

Study sites (26)

CA

DC

FL

KS

MA

MD

MO

NC

NJ

NY

OH

UT

VA

WA