A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer

Inclusion Criteria:

• Phase 1 and Phase 1b lazertinib+Amivantamab combination cohorts: Histologically orcytologically confirmed non-small cell lung cancer (NSCLC) with previously epidermalgrowth factor receptor (EGFR) mutation (identified locally in a Clinical LaboratoryImprovement Amendments [CLIA]-certified laboratory [or equivalent]) that ismetastatic or unresectable, and have progressed after standard of care front-linetherapy, and exhausted available options with targeted therapy. A participant whohas refused all other currently available therapeutic options is allowed to enroll

• For the Phase 1b Lazertinib, Amivantamab and Platinum-doublet Chemotherapy (LACP)combination cohort: histologically or cytologically confirmed advanced or metastaticEGFR-mutated NSCLC who have progressed on or after an EGFR-TKI as the most recentline of treatment with a maximum of 3 prior lines of therapy in the metastaticsetting allowed

• For all expansion cohorts, the EGFR mutation must have been previouslyhistologically or cytologically characterized, as performed by a CLIA-certified (USsites) or an accredited (outside of US) local laboratory, with a copy of themutation analysis being submitted during screening (Phase 1b expansion Cohort B, C,D, E, and F)

1. Expansion Cohort A: Participant must have advanced or metastatic EGFR-mutatednon-small cell lung cancer (NSCLC) that has progressed on prior treatment withosimertinib in the first or second line, followed by progression on aplatinum-based chemotherapy regimen as the last line of therapy prior to studyenrollment. Prior use of first or second generation EGFR tyrosine kinaseinhibitor (TKI) is allowed if administered prior to osimertinib

2. Expansion Cohort B: Participant must have previously treated, advanced ormetastatic NSCLC with documented primary EGFR Exon 20ins activating mutation.Participants should have been treated with standard of care, platinum-basedchemotherapy regimens, but may have treated with approved EGFR TKI,investigational EGFR, or immunotherapy agents if refusing front lineplatinum-based chemotherapy standard of care. Up to 3 lines of prior systemicanti-cancer treatment are allowed

3. Expansion Cohort C: Participant must have advanced or metastatic NSCLCcharacterized by an uncommon activating mutation Additional uncommon EGFRmutations/alterations, beyond those listed above, may be considered forenrollment after agreement with the medical monitor. Participants may betreatment naïve or have been treated with one prior line of therapy which mustbe a first or second generation TKI (that is gefitinib, erlotinib, afatinib) inthe most recent line of therapy. Prior chemotherapy is allowed if administeredprior to EGFR TKI therapy, or as the only systemic anti-cancer therapy prior tostudy enrollment. Up to 2 lines of prior systemic anti-cancer treatment areallowed

4. Expansion Cohort D, E, and F: Participant must have advanced or metastaticEGFR-mutated NSCLC (EGFR Exon19 deletion or L858R) that has progressed on priortreatment with osimertinib in the first or second line (after first- orsecond-generation EGFR TKI), as the immediate prior line of therapy. Onlyprevious treatment in the metastatic setting with a first, second, or thirdgeneration EGFR TKI is allowed. In addition, participants considered forCohorts E and F must be eligible for, and agree to comply with, the use ofprophylactic anticoagulation with a direct oral anticoagulant or a lowmolecular weight heparin during the first 4 months (from Day 1 through Day 120)according to national comprehensive cancer network (NCCN) or local guidelines,if assigned to the combination Cohort E

• Evaluable disease

• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

• Participants must meet the study protocol defined laboratory criteria without havinga history of red blood cell transfusion, platelet transfusion, or granulocyte-colonystimulating factor support within 7 days prior to the date of the test

• A woman of childbearing potential: Must have a negative serum beta human chorionicgonadotropin at screening; Must agree not to breast-feed during the study and for 6months after the last dose of study intervention. (Enrollment is not allowed even ifa woman who is breast-feeding stops breast-feeding); Must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6months after receiving the last dose of study intervention

Exclusion Criteria:

• Participant has an uncontrolled illness, including but not limited to uncontrolleddiabetes, ongoing or active infection (includes infection requiring treatment withantimicrobial therapy [participants will be required to complete antibiotics 1 weekprior to study treatment] or diagnosed or suspected viral infection); activebleeding diathesis; Impaired oxygenation requiring continuous oxygensupplementation; Refractory nausea and vomiting, chronic gastrointestinal diseases,inability to swallow the formulated product, or previous significant bowel resectionthat would preclude adequate absorption of study treatment; or psychiatric illnessor any other circumstances (including social circumstances) that would limitcompliance with study requirements. Any ophthalmologic condition that is eitherclinically unstable or requires treatment

• Prior treatment with anti programmed cell death-1 (PD-1) or anti programmed celldeath-ligand 1 (PD-L1) antibody within 6 weeks of planned first dose of studyintervention

• Untreated brain or other central nervous system (CNS) metastases whether symptomaticor asymptomatic. Participants who have completed definitive therapy, are not onsteroids, and have a stable clinical status for at least 2 weeks prior to studytreatment may be eligible for Phase 1b expansion cohorts. If brain metastases arediagnosed on Screening imaging, the participant may be enrolled, or rescreened foreligibility, after definitive treatment if above criteria are met

• Any Toxicities from prior anticancer therapy must have resolved to commonterminology criteria for adverse events (CTCAE) version 5.0 Grade 1 or baselinelevel (except for alopecia [any grade], Grade <=2 peripheral neuropathy, and Grade <=2 hypothyroidism stable on hormone replacement therapy)

• Allergies, hypersensitivity, or intolerance to Lazertinib or JNJ-61186372 or theirexcipients. For the LACP combination cohort: participant has a contraindication forthe use of carboplatin or pemetrexed (refer to local prescribing information foreach agent). Participant has a history of hypersensitivity to, or cannot take,vitamin B12 or folic acid