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A two-armed antibody that blocks EGFR and its escape partner MET, now first-line for EGFR-mutant lung cancer with lazertinib.
Amivantamab is a low-fucose bispecific IgG1 antibody that binds EGFR and MET at once, with enhanced ADCC and trogocytosis. It is approved for EGFR exon 20 insertion NSCLC (2021, with chemotherapy 2024, PAPILLON), first-line common EGFR mutations with lazertinib (MARIPOSA, 2024; OS benefit shown 2025), and post-osimertinib with chemotherapy (MARIPOSA-2). In MARIPOSA the combination extended progression-free survival to 23.7 versus 16.6 months against osimertinib (HR 0.70) and improved overall survival (HR 0.75). The cost is rash, nail toxicity and venous thromboembolism needing prophylactic anticoagulation; a subcutaneous formulation (2025) reduces infusion reactions. Whether the extra benefit justifies the extra burden is still debated. For a newcomer: the first regimen to beat the standard EGFR pill, at the price of more side effects.
Backbone ribbon from PDB 6WVZ. RCSB PDB 6WVZ. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
Low-fucose bispecific IgG1 blocking EGFR and MET with enhanced ADCC/trogocytosis. Connects to EGFR and MET.
1.Bispecific antibody binds EGFR and MET on the tumour cell
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance: how tumours escape each drug class · Lines of therapy.
Source: US prescribing information (DailyMed). Doses are for orientation; the current label governs.
Given by infusion or injection in a clinic or hospital outpatient department, so it is a Part B drug: Medicare pays 80% after the Part B deductible and the patient owes 20% coinsurance, uncapped in Original Medicare unless a Medigap policy applies. The subcutaneous formulation, if approved, remains clinician-administered and Part B.
Covered under the medical benefit with prior authorisation confirming diagnosis, biomarker status and line of therapy; site-of-care policies may steer infusions away from hospital outpatient departments. EGFR exon 20 insertion or common EGFR mutation documented by an approved test.
20% Part B coinsurance on a high-cost infusion adds up quickly: Medigap Plan G or N, Medicare Advantage maximum out-of-pocket, Medicaid dual eligibility, or a charity fund are the usual buffers.
Sources: Medicare.gov: Chemotherapy · Medicare.gov: Prescription drugs (outpatient, Part B). Not medical or financial advice; verify with your plan.
Sources: NICE TA1122. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
Treatment of adult patients with locally advanced or metastatic non small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA approved test, whose disease has progressed on or after platinum based chemotherapy
Accelerated approval, EGFR exon 20 insertion NSCLC after platinum source
Treatment of adult patients with locally advanced or metastatic non small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA approved test, whose disease has progressed on or after platinum based chemotherapy
First-line exon 20 insertion with chemotherapy (PAPILLON) source
First-line EGFR-mutant NSCLC with lazertinib (MARIPOSA) source
After osimertinib, with chemotherapy (MARIPOSA-2) source
Subcutaneous formulation (PALOMA-3) source
| Region | Year | Indication |
|---|---|---|
| US | 2021 | EGFR exon 20 insertion NSCLC |
| US | 2024 | First-line EGFR-mutant NSCLC with lazertinib |
| EU | 2021 | Exon 20; 1L with lazertinib Jan 2025 |
| England (NICE) | 2022 | Locally advanced or metastatic non-small-cell lung cancer with an EGFR exon 20 insertion after platinum-based chemotherapy: not recommended · TA850, published 14 December 2022, does not recommend amivantamab, so the second-line indication is not funded in England. |
| England (NICE) | 2026 | Untreated advanced EGFR mutation-positive non-small-cell lung cancer (exon 19 deletion or L858R), with lazertinib · TA1122, published 21 January 2026 (MARIPOSA); must be funded in England within 90 days of publication. |
| England (NICE) | 2026 | Untreated advanced non-small-cell lung cancer with an activating EGFR exon 20 insertion, with carboplatin and pemetrexed · TA1158, published 28 May 2026, available during a managed access period under a managed access agreement (PAPILLON). |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Rash | 86% | 26% |
| Nail toxicity | 71% | 11% |
| Infusion-related reaction | 63% | 6% |
| Musculoskeletal pain | 47% | 2.1% |
| Oedema | 43% | 2.6% |
| Stomatitis | 43% | 2.4% |
| Venous thromboembolism | 36% | 11% |
| Paraesthesia | 35% | 1.7% |
MARIPOSA, with lazertinib. Rates read from the US prescribing information. Blank cells mean the figure was not sourced, not that it is zero.
| Country | Reimbursement | List price | Assistance |
|---|---|---|---|
| United States | Medicare Part B (physician-administered); commercial plans per formulary | not disclosed | janssencarepath.com |
| United Kingdom | NICE: recommended with lazertinib for untreated EGFR-mutant NSCLC (2025) and exon 20 insertion after platinum | not disclosed | - |
List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.
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Query for this drug: (TITLE:"Amivantamab" OR ABSTRACT:"Amivantamab" OR TITLE:"Rybrevant" OR ABSTRACT:"Rybrevant") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Amivantamab, not a curated reading list.
Shares EGFR TKI → ADC on progression, A Study to Investigate Safety and Efficacy of Osimertinib and Amivantamab in Participants With Non-small Cell Lung Cancer With Common Epidermal Growth, Dae Ho Lee, Amivantamab + lazertinib (first-line EGFR NSCLC).
Shares Amivantamab + lazertinib (first-line EGFR NSCLC), Drug-tolerant persister cells, Resistance routes: how a blocked pathway comes back, Receptor tyrosine kinase activation.
Shares Add a drug when the blood test turns, without stopping the one that works, Byoung Chul Cho, MARIPOSA, Add the second drug on day one when the escape route is predictable.
Shares MET amplification (gene copy number), MET amplification (bypass resistance), MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer, Resistance routes: how a blocked pathway comes back.
Shares EGFR exon 20 insertion, EGFR L858R, EGFR exon 19 deletion, Non-small cell lung cancer (KEGG map).
Shares MET amplification (gene copy number), MET amplification (bypass resistance), Non-small cell lung cancer (KEGG map), MET exon 14 and MET-amplified non-small-cell lung cancer.
Shares MET amplification (gene copy number), MET amplification (bypass resistance), Resistance routes: how a blocked pathway comes back, MET.
Shares MET amplification (gene copy number), MET amplification (bypass resistance), Resistance routes: how a blocked pathway comes back, MET.