Medical oncologists and thoracic oncology teams managing patients with newly diagnosed EGFR exon 19 deletion or exon 21 L858R substitution mutation-positive locally advanced or metastatic NSCLC should consider the MARIPOSA data when selecting first-line systemic therapy given the reported PFS advantage of lazertinib plus amivantamab versus osimertinib ^[3]. For patients without EGFR or ALK genomic aberrations, subcutaneous KEYTRUDA QLEX represents an alternative route of administration for pembrolizumab with reported ORR comparable to intravenous pembrolizumab in Study MK-3475A-D77; selection for single-agent pembrolizumab requires PD-L1 TPS ≥1% as determined by an FDA-authorized test ^[4][1]. When using amivantamab subcutaneous or the lazertinib combination, clinicians should follow label recommendations regarding baseline bodyweight–based dosing, the recommendation for prophylactic anticoagulation for the first four months in the lazertinib plus amivantamab regimen, and embryo-fetal toxicity counseling ^[2][3].

Q1 What is the drug approved for?

A1 Lazertinib in combination with amivantamab is indicated for the first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test, based on MARIPOSA trial results showing improved progression-free survival compared to osimertinib. Amivantamab and hyaluronidase-lpuj for subcutaneous injection (Rybrevant Faspro) was approved to provide a subcutaneous formulation for the adult indications approved for the intravenous formulation of amivantamab; full prescribing information lists specific indications and dosing by indication. KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) is approved for multiple indications including first-line treatment of metastatic nonsquamous NSCLC without EGFR or ALK genomic tumor aberrations in combination with pemetrexed and platinum chemotherapy, and as a single agent for first-line treatment of NSCLC expressing PD-L1 TPS ≥1% with no EGFR or ALK aberrations.

Q2 How does it work?

A2 Pembrolizumab (in KEYTRUDA QLEX) is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response; berahyaluronidase alfa is an endoglycosidase that temporarily increases subcutaneous tissue permeability by depolymerizing hyaluronan to enable subcutaneous administration of pembrolizumab. Information on the precise mechanisms of action for amivantamab or lazertinib was not available in the provided source excerpts.

Q3 What is the dose?

A3 The recommended lazertinib dose in the approved combination with amivantamab is 240 mg orally once daily administered in combination with amivantamab with or without food; the recommended amivantamab dose is based on baseline bodyweight and depends on the specific indication, with subcutaneous amivantamab dosing described in the prescribing information for Rybrevant Faspro. For KEYTRUDA QLEX the recommended adult dose for patients >40 kg is either every 3-week dosing (395 mg/4,800 units; inject 2.4 mL subcutaneously over 1 minute) or every 6-week dosing (790 mg/9,600 units; inject 4.8 mL subcutaneously over 2 minutes) depending on schedule and indication; KEYTRUDA QLEX must be administered by a healthcare provider and not intravenously. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the side effects?

A4 Reported and labeled adverse reactions include immune-mediated adverse reactions such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic events, and the potential for solid organ transplant rejection with pembrolizumab-containing regimens; the most common adverse reactions (≥20%) with KEYTRUDA QLEX plus chemotherapy were nausea, fatigue, and musculoskeletal pain. Amivantamab subcutaneous labeling includes warnings for hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, venous thromboembolic events when used with lazertinib (with a recommendation for prophylactic anticoagulation for the first four months of therapy in the lazertinib combination), dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.