A phase I/II trial of the safety and clinical activity of a HER2-protein based immunotherapeutic for treating women with HER2-positive metastatic breast cancer

Abstract

The objectives of this phase I/II study (NCT00140738) were to evaluate the safety and clinical activity of a cancer immunotherapeutic agent (recombinant HER2 protein (dHER2) and the immunostimulant AS15) in patients with HER2-overexpressing metastatic breast cancer (MBC). Forty HER2-positive MBC patients received up to 18 doses (12q2w, 6q3w) of dHER2 immunotherapeutic, as first- or second-line therapy following response to trastuzumab-based treatment as maintenance. Toxicity was graded by the Common Terminology Criteria for Adverse Events (CTCAE) and clinical activity was evaluated by target lesion assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST). Immunogenicity was assessed. The dHER2 immunotherapeutic was well tolerated: grade 1/2 adverse events (AEs) were most common. No cardiac events were observed and one patient experienced an asymptomatic decrease of left ventricular ejection fraction below the normal range (47 %). Both humoral and cellular immunogenicity to the dHER2 antigen was observed. No patient discontinued the immunizations because of AEs but 35/40 withdrew prematurely, 34 because of disease progression (24/34 before or at the tumor assessment after dose 6). One patient achieved a complete response lasting 11 months and one patient had a partial response lasting 3.5 months. Ten patients experienced stable disease ≥26 weeks with 4/10 still in stable disease at the last tumor assessment after 47 weeks. Immunization of MBC patients with the dHER2 immunotherapeutic was associated with minimal toxicity and no cardiac events. Clinical activity was observed with two objective responses and prolonged stable disease for 10/40 patients.

Safety and Immunogenicity of a Human Epidermal Growth Factor Receptor 1 (HER1)-Based Vaccine in Prostate Castration-Resistant Carcinoma Patients: A Dose-Escalation Phase I Study Trial

“…This finding was confirmed with larger patient sample in the recently finished phase III clinical trial (manuscript in preparation). Another exploratory study using a HER2 protein-based vaccine in HER2+ metastatic breast cancer patients found that a longer progression-free-survival time was observed for patients with high anti-HER2-ECD antibodies concentrations compared to low antibody response (Curigliano et al, 2016). In addition, in a phase III clinical trial in which Sipuleucel T was administered to CRPC patients, IgG response to PSAs was associated with improved OS in vaccinated patients (GuhaThakurta et al, 2015).…”

Developing anti‐HER2 vaccines: Breast cancer experience

“…The response increased with increasing doses and frequency of vaccination. In another recent Phase I/II study with recombinant dHER2 plus AS15 in patients with HER2‐overexpressing metastatic breast cancer as first‐ or second‐line therapy after response to trastuzumab‐based treatment as maintenance, 1 of 40 patients achieved complete remission lasting for 11 months, and 1 of 40 patients had a partial response for 3.5 months according to RECIST . Humoral and cellular immunity to the dHER2 antigen was demonstrated, and 10 of 40 patients achieved prolonged stable disease.…”

“…Humoral and cellular immunity to the dHER2 antigen was demonstrated, and 10 of 40 patients achieved prolonged stable disease. The vaccine was well tolerated with minimal adverse reactions . The trial also evaluated dHER2 in combination with lapatinib (NCT00952692).…”

Gastric cancer management: Kinases as a target therapy

“…Current advances include the development of immunotherapeutic vaccines, such as the dHer2 vaccine, which is aimed at inducing comprehensive anti‐Her2 immunity and is in clinical testing for breast cancer treatment. It has reached phase I/II trials and was shown to be safe and well tolerated …”