Pertuzumab

About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.

Abstract P2-11-03: Phase I/II randomized study of combination immunotherapy with or without polysaccharide krestin (PSK) concurrently with a HER2 ICD peptide-based vaccine in patients with stage IV breast cancer receiving HER2-targeted monoclonal antibody therapy

Abstract: Natural killer (NK) cell defects, commonly seen in metastatic breast cancer (MBC) lead to decrease in dendritic cell (DC) maturation, proinflammatory cytokine production, and tumor infiltrating T-cells (TILs). This results in a protumorigenic Th2 immune microenvironment with low response rates to immunotherapy (i.e., immune checkpoint blockade) and standard chemotherapy. PSK, a potent TLR-2 agonist, activates NK cells to produce IFN-γ and IL-12 and promote DC maturation/differentiation toward a Th1 profile in the tumor microenvironment which results in antigen specific TIL that can eradicate tumor. The combination immunotherapy of PSK and HER2 directed therapy described here, aims at inducing Th1 immunity and tumor specific T-cells. This proposed regimen could eradicate microscopic residual disease and prevent recurrence in optimally treated HER2+ MBC patients. Moreover, the regimen could result in enhanced trafficking of TILs to the site of tumor and improve the efficacy of checkpoint inhibitors and other therapies. A phase I/II randomized 2 arm study of combination immunotherapy with oral PSK (or placebo) given with a HER2 peptide vaccine and HER2 mAb therapy (trastuzumab (TZ) +/- pertuzumab (PZ)) was initiated to assess the safety of the approach and evaluate the effect of PSK on NK cell activity, pro-inflammatory cytokine/chemokine profile; and HER2 vaccine-induced T cell immunity. Methods: Up to 30 patients with HER2+ MBC who are without evidence of disease after definitive therapy and currently on maintenance TZ +/- PZ are enrolled and randomly assigned in equal numbers to 1 of 2 arms (15 patients/arm): Arm 1: HER2 ICD vaccine + placebo or Arm 2: HER2 ICD vaccine + PSK. All patients receive concomitant treatment with 4 months of daily oral PSK or placebo, 3 monthly intradermal HER2 ICD vaccinations and continued TZ +/- PZ. Toxicity is evaluated per CTEP CTCAE 4.0, during and post vaccination. Serial blood draws for immunologic evaluation of NK cell activity and antigen-specific T cell immunity via flow cytometry and IFN-γ ELISPOT, respectively; and pro-inflammatory cytokines/chemokines. Results: 24 subjects have been enrolled and 60 vaccines have been given. 16 subjects have completed all 3 vaccines and PSK/placebo; and 6 subjects are currently in progress. 2 subjects received Conclusion: Combination immunotherapy with PSK/placebo and concurrent HER2 directed therapy is safe and well-tolerated. Further ongoing immunologic studies will help define the immunogenicity of the approach. Citation Format: Salazar LG, Higgins D, Childs J, Coveler AL, Liao J, Stanton S, Gooley T, Standish LJ, Sasagawa M, DISIS ML. Phase I/II randomized study of combination immunotherapy with or without polysaccharide krestin (PSK) concurrently with a HER2 ICD peptide-based vaccine in patients with stage IV breast cancer receiving HER2-targeted monoclonal antibody therapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-11-03.

Development of antibody drugs targeting against HER2 for cancer therapy

Abstract: Human epidermal growth factor receptor 2 (HER2) belongs to the transmembrane glycoprotein receptor family. Overexpression of HER2 could directly lead to tumorigenesis and metastasis. This phenomenon could be observed in the breast cancer, ovarian cancer, gastric cancer, lung cancer and prostate cancer. Compared with the conventional chemotherapy, the targeted treatment of antibody is more specific and has lower side effects. This review describes the current status of monotherapy and combination therapies of anti-HER2 antibodies, trastuzumab and pertuzumab, with chemotherapeutic drugs. The development trends of new formats of anti-HER2 antibody drugs such as bispecific antibody, immunotoxin are also discussed.

Prevalence of hypomagnesemia in patients with HER2–positive breast cancer receiving pertuzumab treatment.

Abstract: e11608 Background: Human Epidermal growth factor Receptor-2 (HER2) is a member of the epidermal growth factor (EGFR) family of transmembrane receptors and is overexpressed in ~20% of breast cancers...

Abstract P5-21-26: T-DM1 activity in metastatic HER2-positive breast cancer patients who have received prior trastuzumab and pertuzumab: NSABP B-005

Abstract: Background : The pivotal phase III EMILIA trial reported a progression free survival (PFS) rate of 9.6 months and an objective response rate of 43% with T-DM1 in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. However, there is very limited data on the efficacy of T-DM1 in patients who have received prior pertuzumab either neoadjuvantly or as first line therapy in the metastatic setting. The primary goal of this study was to assess the clinical efficacy (tumor response rates and median duration on therapy) of T-DM1 in patients previously treated with pertuzumab and trastuzumab. Methods: After IRB approval, a cancer data registry and electronic pharmacy database were utilized to identify breast cancer patients receiving treatment with T-DM1 at Cleveland Clinic and University of Pittsburgh. Patients that received trastuzumab and pertuzumab, in either the neoadjuvant or metastatic setting, with baseline and follow up imaging available for review were identified. Patient charts were reviewed to collect accurate information about the treatment sequencing and outcomes. RECIST version 1.1 was utilized for tumor assessment and patients with measurable disease and non measurable disease were included in the study. Results: We identified a total of 23 patients with a median age of 55 years that met the inclusion criteria. 69% percent of patients received T-DM1 as first line or second line therapy and 31% received it as third line or later. All patients had at least 1 measurable lesion. Best overall response showed rates of complete response, partial response and stable disease of 17%, 26% and 22% respectively. 35% patients progressed on first assessment after start of treatment. The median duration on therapy was 5.3 months (range 3 weeks to 33 months) with 43% of patients receiving T-DM1 for greater than 6 months. Conclusion: Our results were comparable to those reported by EMILIA trial. T-DM1 has reasonable clinical efficacy in patients who have received prior treatment with pertuzumab and trastuzumab with an overall response rate of 43% and median duration on therapy of 5.3 months. Citation Format: Tiwari SR, Sussman T, Kota K, Moore HC, Montero AJ, Budd GT, Puhalha S, Abraham J. T-DM1 activity in metastatic HER2-positive breast cancer patients who have received prior trastuzumab and pertuzumab: NSABP B-005 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-26.

Evaluation of biosimilar trastuzumab MYL-1401O in HER2-positive breast cancer.

Abstract: OBJECTIVES The trastuzumab biosimilar MYL-1401O has demonstrated equivalent efficacy and comparable safety to reference trastuzumab (RTZ) in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) as HER2 monotherapy. STUDY DESIGN Here, we present the first real-world comparison of MYL-1401O vs RTZ as single/dual HER2-targeted therapy for the neoadjuvant, adjuvant, and palliative treatment of HER2-positive breast cancer in the first and second lines. METHODS We retrospectively investigated medical records. We identified patients with HER2-positive early-stage breast cancer (EBC) (n = 159) who had received neoadjuvant chemotherapy with RTZ or MYL-1401O ± pertuzumab (n = 92) or adjuvant chemotherapy with RTZ or MYL-1401O plus taxane (n = 67) between January 2018 and June 2021, as well as patients with MBC (n = 53) who had received palliative first-line treatment with RTZ or MYL-1401O and docetaxel ± pertuzumab or second-line treatment with RTZ or MYL-1401O and taxane between January 2018 and June 2021. RESULTS The rate of achieving pathologic complete response in patients receiving neoadjuvant chemotherapy was similar between those receiving MYL-1401O and RTZ (62.7% [37/59] and 55.9% [19/34], respectively; P = .509). Progression-free survival (PFS) at 12, 24, and 36 months was similar in the 2 cohorts of the EBC-adjuvant group: 96.3%, 84.7%, and 71.5%, respectively, in patients receiving MYL-1401O, and 100%, 88.5%, and 64.8% in patients receiving RTZ (P = .577). Median PFS was also similar in MBC, at 23.0 months (95% CI, 9.8-26.1) in patients receiving MYL-1401O and 23.0 months (95% CI, 19.9-26.0) in patients receiving RTZ (P = .270). The overall response rate, disease control rate, and cardiac safety profiles did not show significant differences in efficacy outcomes between the 2 groups. CONCLUSIONS These data suggest that biosimilar trastuzumab MYL-1401O has similar effectiveness and cardiac safety to RTZ in patients with HER2-positive EBC or MBC.