| General information |
| Database: | DB00708 |
| Objective: | Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER2 receptor and blocks its ability to dimerize with other HER receptors. Pertuzumab represents a new class of targeted therapeutics known as HER dimerization inhibitors. A clinical study was conducted to investigate safety and pharmacokinetics of pertuzumab and to perform a preliminary assessment of HER dimerization inhibition as a treatment strategy. |
| Authors: | Agus DB, et al |
| Title: | Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2005 |
| PMID: | 15699478 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | Pertuzumab
|
| Target: | Receptor proteintyrosine kinase erbB2
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | Advanced Cancer Location of primary tumor Breast Colorectal Lung Ovarian Pancreas Prostate Sarcoma Adenocarcinoma of unknown origin |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I Clinical Study |
| Key Patients Feature: | The study population consisted of patients with incurable, locally advanced, recurrent or metastatic solid tumors that hadprogressed during or after standard therapy. All patients gavewritten informed consent and the protocol was revietheyd and approved by institutional review boards at participating institutions. Patients enrolled onto the study were at least 18 years old, with an Eastern Cooperative Group performance status of0 or 1, and a life expectancy of at least 12 weeks. Other inclusioncriteria were: histologic documentation of malignancy; at leastone bidimensionally measurable lesion (except for patientswith prostate cancer and ovarian cancer in whom rises in prostatespecific antigen [PSA] and CA125, respectively, were allowed); HER2negative status in patients with breast cancer;and adequate hematology, liver function, and biochemistry tests(neutrophils $ 1.5 109/L, platelets $ 100 109/L, hemoglobin$ 9 g/dL; serum bilirubin # upper limit of normal [ULN] andalkaline phosphatase, AST and ALT # 2.5 ULN, except in patients with liver or bone metastases [ALT, AST, and alkalinephosphatase # 5 ULN]; serum creatinine # ULN, or creatinine clearance $ 60 mL/min; international normalized ratio 1.3 and activated partial thromboplastin time 1.5 ULN). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts were recruited to a doseescalation study of pertuzumab (0.5 to 15 mg/kg) given intravenously every 3 weeks. |
| Primary End Point: | safety and tolerability; pharmacokinetics;an optimal dose and schedule for phase II testing. |
| Secondary End Point: | a preliminary assessment of clinical response to pertuzumab was made |
| Patients Number: | 21 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Two patients, one with ovarian cancer (5.0 mg/kg) and onewith pancreatic islet cell carcinoma (15.0 mg/kg), achieved a partial response. Responseswere documented by Response Evaluation Criteria in Solid Tumors after 1.5 and 6 monthsof pertuzumab therapy, and lasted for 11 and 10 months, respectively. Stable disease lastingfor more than 2.5 months (range, 2.6 to 5.5 months) was observed in six patients |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events were asthenia (62%), vomiting (52%), nausea (48%), abdominal pain (48%), rash (43%), diarrhea (43%), pain (43%), and anemia (33%), most of which were either grade 1 or grade 2 in severity. |
| Conclusions: | These results demonstrate that pertuzumab is well tolerated, has a pharmacokinetic profile which supports 3week dosing, and is clinically active, suggesting that inhibition of dimerization may be an effective anticancer strategy. |