ORCHARD: Osimertinib Plus Necitumumab in Patients With Epidermal Growth Factor Receptor-Mutated Advanced Non-Small Cell Lung Cancer With a Secondary Epidermal Growth Factor Receptor Alteration Whose Disease Had Progressed on First-Line Osimertinib
Published report from the ORCHARD trial registered as NCT03944772, in JCO Precision Oncology (2025), chosen as the most cited paper whose own text cites the registry id.
Overview
Purpose: ORCHARD (ClinicalTrials.gov identifier: NCT03944772) is a phase II, biomarker-directed platform study designed to characterize resistance mechanisms and evaluate novel drug combinations in patients with epidermal growth factor receptor ( EGFR)-mutated advanced non-small cell lung cancer who have progressed on first-line osimertinib. We report final results of the module assessing the efficacy and safety of osimertinib plus necitumumab (a monoclonal antibody that blocks EGFR) in patients with ≥one of the following: EGFR amplification or select secondary EGFR alterations (L718 or G724 mutation, or exon 20 insertion).
Materials and methods: Patients received osimertinib (80 mg orally once daily) plus necitumumab (800 mg intravenously, days 1 and 8 of a 3-week cycle) until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST 1.1 by investigator assessment.
Results: Overall, 19 patients received osimertinib plus necitumumab; at data cutoff (April 18, 2023), all patients had discontinued treatment. The ORR was 11% (80% CI, 3 to 26); two patients had a confirmed partial response, with duration of response of 10.4 and 6.0 months; both patients had EGFR amplification. The median progression-free survival was 4.0 months (95% CI, 1.3 to 5.4) and the overall survival was 11.4 months (95% CI, 6.6 to 15.5). Ten patients (53%) had grade ≥3 adverse events, most commonly embolism (not otherwise specified, pulmonary embolism or deep vein thrombosis, reported in four patients; 21%). The safety profile of the combination was consistent with the known profiles of the two individual drugs, and no new signals were identified.
Conclusion: Osimertinib plus necitumumab demonstrated modest clinical benefit, and the overall risk-benefit analysis indicates that further evaluation of the regimen is not warranted in these molecularly defined subsets of osimertinib resistance.
Indexed on Europe PMC as PubMed record 40466026 (DOI 10.1200/po-24-00818). Its abstract cites the registry id NCT03944772, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT03944772 with the most citations, so it is the natural first reading for anyone following the ORCHARD trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.