Commentary

Video

Dr Davis on the Investigation of Neratinib Plus Trastuzumab Deruxtecan in Advanced HER2+ Solid Tumors

Andrew Davis, MD, discusses an ongoing phase 1 trial combining neratinib and trastuzumab deruxtecan in metastatic HER2-positive solid tumors.

Andrew Davis, MD, assistant professor of medicine, Division of Medical Oncology, Washington University School of Medicine, medical oncologist, Siteman Cancer Center, discusses an ongoing phase 1 trial (NCT05372614) investigating the combination of neratinib and fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with metastatic HER2-positive solid tumors.

The trial is examining the safety and efficacy of combining the antibody-drug conjugate (ADC) trastuzumab deruxtecan with neratinib, an oral TKI, Davis begins. This study was designed based on preclinical evidence derived from work by Ron Bose, MD, PhD, of Siteman Cancer Center, showing that neratinib enhanced the uptake of trastuzumab deruxtecan in patient-derived xenograft models of HER2-mutated, HER2–non-overexpressing breast cancer, he adds.

The phase 1 trial is including patients with metastatic solid tumors harboring HER2-overexpression(immunohistochemistry 3+), ERBB2 amplifications, or activating HER2 mutations. Patients must have received at least 1 prior line of systemic therapy in the advanced setting to enroll.

The primary objectives are to assess safety and tolerability of the combination, and secondary objectives include evaluating pharmacokinetics, preliminary efficacy, and potential biomarkers of response.

Davis emphasizes that understanding the interaction between ADCs and TKIs could lead to enhanced efficacy without significant additional toxicity. The data generated from this trial will provide critical insights into the combination therapy's safety profile and its potential to improve outcomes for patients with metastatic HER2-positive solid tumors, he explains.

There remains a need for more data regarding ADC-based combinations in the treatment of patients with solid tumors, and findings from this trial could help inform these types of approaches, Davis concludes.

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