A Study of Neoadjuvant Amivantamab With Either Lazertinib or Chemotherapy in Participants With Resectable EGFR-Mutated NSCLC

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Participant must have histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC) with completely resectable Stage II-IIIB N2 disease
• Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a multidisciplinary team evaluation
• Participant must consent to a screening biopsy, if clinically feasible, if no adequate tumor tissue is available for a baseline sample
• Participant 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). Prior or concurrent second malignancies must be reviewed and agreed to with the medical monitor
• Have an eastern cooperative oncology group (ECOG) performance status of 0 or 1

You cannot join if

• History of uncontrolled illness
• Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current interstitial lung disease (ILD)/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
• Suspected or known allergies, hypersensitivity, or intolerance to excipients of: the combination of amivantamab and lazertinib or carboplatin and pemetrexed
• Presence of primary driver mutations (anaplastic lymphoma kinase [ALK], mesenchymal-epithelial transition [MET], human epidermal growth factor receptor 2 [HER2], proto-oncogene tyrosine-protein kinase ROS [ROS1], neurotrophic tyrosine receptor kinase [NTRK], B-Raf proto-oncogene [BRAF], REarranged during transfection [RET], or kirsten rat sarcoma viral oncogene homolog [KRAS]) , besides EGFR Exon 19del or Exon 21 L858R mutations, as determined by local genomic testing
• Prior treatment with any systemic anti-cancer therapy for NSCLC including EGFR-tyrosine kinase inhibitor (TKI) therapy, chemotherapy, biologic therapy, immunotherapy, or any investigational drug

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

amivantamab and recombinant human hyaluronidase. A co-formulation composed of amivantamab, a human bispecific antibody targeting both epidermal growth factor receptor EGFR and hepatocyte growth factor receptor (HGFR; c-Met), and a recombinant form of human hyaluronidase, with potential antineoplastic activity. Upon subcutaneous administration of amivantamab and recombinant human hyaluronidase, the hyaluronidase reversibly depolymerizes the polysaccharide hyaluronan in the subcutaneous tissue. This increases the permeability of the subcutaneous tissue and enhances the absorption of amivantamab into the systemic circulation. In turn, amivantamab simultaneously targets and binds to wild-type or certain mutant forms of both EGFR and c-Met expressed on cancer cells, thereby preventing receptor phosphorylation. This prevents the activation of both EGFR- and c-Met-mediated signaling pathways. In addition, binding results in receptor degradation, which further inhibits EGFR- and c-Met-mediated signaling. Amivantamab also causes antibody-dependent cellular cytotoxicity (ADCC). Altogether, this results in the inhibition of tumor cell proliferation. When administered subcutaneously, hyaluronidase, an endoglycosidase, increases the dispersion and absorption of co-administered drugs. EGFR and c-Met, upregulated or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation. NCI Drug Dictionary

lazertinib mesylate hydrate. The hydrated mesylate salt form of lazertinib, an orally available third-generation, selective inhibitor of certain forms of the epidermal growth factor receptor (EGFR) with activating mutations, including the resistance mutation T790M, exon 19 deletions (Del19), and the L858R mutation, with potential antineoplastic activity. Upon oral administration, lazertinib specifically and irreversibly binds to and inhibits selective EGFR mutants, specifically EGFR exon 19 deletions and exon 21 L858R substitution mutations. This prevents EGFR mutant-mediated signaling and leads to cell death in EGFR mutant-expressing tumor cells. In addition, lazertinib penetrates the blood-brain barrier (BBB). As this agent shows minimal activity against wild-type EGFR (wtEGFR), systemic toxicity is minimal as compared to non-selective EGFR inhibitors. EGFR, a receptor tyrosine kinase (RTK) mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. NCI Drug Dictionary

Treatments listed in the registry

• Amivantamab (Drug): Amivantamab will be administered.
• Lazertinib (Drug): Lazertinib will be administered.
• Carboplatin (Drug): Carboplatin will be administered.
• Pemetrexed (Drug): Pemetrexed will be administered.

Non Randomized · Parallel · masking: None

Main goals

• Major Pathologic response (MPR) (Up to 1 year 8 months)

Other goals

• Pathological Complete Response (pCR)
• Number of Participants with Pathologic Nodal Downstaging at the Time of Surgery
• Disease Control Rate (DCR)
• Number of Participants with Adverse Events (AEs) by Severity
• Number of Participants with Abnormalities in Clinical Laboratory Parameters

Planned enrollment: 68 (estimated).

• City of Hope, Duarte, California
• City of Hope 1, Irvine, California
• Providence Cancer Center, Portland, Oregon
• Providence Oncology and Hematology Care Clinic Westside, Portland, Oregon

19 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07586202
• NCI Drug Dictionary: C124993
• NCI Drug Dictionary: C210427

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 24, 2026. Public record; not medical advice.