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).
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 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
Parallel
Amivantamab
DrugAmivantamab will be administered subcutaneously by manual injection.
Lazertinib
DrugLazertinib will be administered as an oral tablet.
Carboplatin
DrugCarboplatin will be administrated by IV infusion.
Pemetrexed
DrugPemetrexed will be administered by IV infusion.
Direct Oral Anticoagulant (DOAC)
DrugDOAC will be administered orally.
Low Molecular Weight Heparin (LMWH)
DrugLMWH will be administered subcutaneously.
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Treatment groupsSee each treatment group below.
All Cohorts Except Cohort 4: Objective Response Rate (ORR) Based on Investigator Assessment (INV)
ORR based on INV will be reported. ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by investigator.
Cohort 4: Number of Participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
Cohort 4: Number of Participants with AEs by Severity
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values
Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.
All Cohorts Except Cohort 4: Number of Participants with AEs
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
All Cohorts Except Cohort 4: Number of Participants with AEs by Severity
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values
Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.
All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity
Number of participants with abnormalities in clinical laboratory values which includes serum chemistry, hematology, coagulation, urinalysis, and serology) by severity will be reported. Severity of laboratory values abnormalities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
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