Somatic mutations in HER2 (ERBB2), in the absence of HER2 amplification, are oncogenic and occur in ∼3% to 5% of solid tumors. HER-Seq (PUMA-NER-9501; ClinicalTrials.gov NCT03786107) is an international genomic screening study for the identification of patients with HER2-mutant breast or cervical cancer, who may be eligible for neratinib clinical trials. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has reported clinical activity in HER2-mutant cancers, with the greatest efficacy observed in breast and cervical cancer. The ongoing Phase II SUMMIT trial for HER2-mutant cancers examines the safety and efficacy of neratinib as monotherapy or in combination (ClinicalTrials.gov NCT01953926; EudraCT 2013-002872-42). Identification of somatic HER2 mutations using a rapid and minimally-invasive test offers a novel therapeutic opportunity for this rare molecular cancer subtype.
Patients with histologically-confirmed metastatic breast cancer (MBC) or metastatic cervical cancer (MCC) on active treatment or in follow-up, may be enrolled. Blood samples are collected for circulating tumor DNA (ctDNA) analysis at 3–6-month intervals (coincident with scheduled patient visits). Samples are sequenced centrally for the detection of somatic HER2 mutations, using a custom targeted next-generation sequencing (NGS) assay. Patients found to have a mutation in HER2 are then eligible to screen for therapeutic studies with neratinib. Eligible patients are ≥18 years of age with histologically-confirmed MBC or MCC, an ECOG status of 0–2, and are able to provide blood samples. Excluded are patients with known HER2-positive/HER2-amplified MBC, or those who have previously received neratinib.
Lee Miller (Miller Medical Communications Ltd).
NCT03786107.
Puma Biotechnology Inc.
Puma Biotechnology Inc.
L.M. Smyth: Consulting or advisory role: Roche Genentech, AstraZenaca; Research funding (Inst): Puma Biotechnology, AstraZeneca, Roche Genentech; Travel, accommodations, expenses: Pfizer; Honoraria: Pfizer, AstraZeneca. C. Saura: Consulting fees: Puma Biotechnology Inc. V. Boni: Consulting/advisory board: Loxo therapeutics, Ideya. L. Eli, S.J. Garza: Employee: Puma Biotechnology Inc. A.S. Lalani: Employee, shareholder: Puma Biotechnology Inc. All other authors have declared no conflicts of interest.