Trial-by-gene · EGFR

Active clinical trials enrolling EGFR-mutant NSCLC

Decision-support aid only — eligibility decisions must be confirmed against the actual trial protocol and the patient's medical record. Trial counts and statuses change daily; this page is for orientation, not adjudication.

EGFR-mutant NSCLC has the most mature targeted-therapy landscape of any solid tumor. Active trials concentrate on three frontiers: (1) post-osimertinib resistance, including MET-amplification co-targeting (amivantamab + lazertinib, MARIPOSA, MARIPOSA-2), (2) the distinct exon 20 insertion subset (amivantamab + chemo, mobocertinib historical, newer agents), and (3) CNS metastasis prevention and treatment.

For variant-aware trial matching at the patient level, see the EGFR cheat sheet for the underlying biology, and Engine 1 for the API-level trial-matching capability that powers automated routing.

Browse the live listing

Search ClinicalTrials.gov for actively recruiting NSCLC trials with EGFR-targeted interventions or biomarker eligibility.

Open ClinicalTrials.gov listing

Source: ClinicalTrials.gov, US National Library of Medicine. Trial-listing data is in the public domain. Use of ClinicalTrials.gov data must comply with the NLM terms of use.

Representative trial phases and designs

Phase III, post-osimertinib

MET-amplification co-targeting after osimertinib progression — amivantamab + lazertinib + chemotherapy vs chemotherapy alone.

Example: NCT04988295

Phase III, exon 20 insertions

First-line amivantamab + chemotherapy vs chemotherapy for unresectable EGFR exon 20 insertion NSCLC (PAPILLON).

Example: NCT04538664

Phase II, brain metastases

Dedicated osimertinib trials in patients with active CNS disease, often paired with stereotactic radiotherapy.

Phase I/II, ADC platforms

HER3-DXd (patritumab deruxtecan) and other ADC trials enrolling EGFR-mutant NSCLC post-TKI.

Example: NCT04619004

Eligibility notes

Most EGFR-mutant NSCLC trials require documented activating EGFR mutation (L858R, exon 19 del, T790M, or exon 20 insertion depending on study). Specific trials further stratify by prior osimertinib, prior chemotherapy, CNS disease status, ECOG PS, and biomarker co-features (MET amplification, HER3 expression). Confirm against the actual protocol.

Frequently asked questions

Are post-osimertinib trials only for patients with documented resistance?
Most require radiographic progression on prior osimertinib (or other 1st/2nd-gen TKI), plus documentation of the resistance mechanism in some protocols (MET amplification by NGS or IHC). A subset of trials enroll based on progression alone.
Which trials enroll exon 20 insertion patients?
Amivantamab-based trials and ADC platforms have the most exon-20-insertion-specific enrollment. EGFR TKI trials usually exclude exon 20 insertions because the mutations respond poorly to classical TKIs.

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