| General information |
| Database: | DB00686 |
| Objective: | Thisphase IIIa study was designed to identify the maximum tolerated dose (MTD) and assess safety, antitumour activity, pharmacokinetics and pharmacodynamics of BMS690514. |
| Authors: | Soria JC, et al |
| Title: | Phase IIIa study of BMS690514, an EGFR, HER2 and 4 and VEGFR1 to 3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours. |
| Journal: | Eur J Cancer. |
| Year: | 2013 |
| PMID: | 23490650 |
| Trial Design |
| Clinical Trial Id: | NCT00329004 |
| Agent: | BMS690514
|
| Target: | epidermal growth factor receptor (EGFR/HER1), HER2 and 4, and vascular endothelial growth factor receptors (VEGFRs)1 to 3
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I-IIa study |
| Key Patients Feature: | Phase I included patients aged P18 years withadvanced or metastatic solid tumours without brainmetastasis for whom the standard of care was ineffectiveor inappropriate. Other inclusion criteria included anEastern Cooperative Oncology Group performance status 0-1, adequate bone marrow function and life expectancy P12 weeks. Previous chemotherapy, hormonaltherapy, immunotherapy, antibodytargeted or othertargeted therapy (including prior exposure to eitherVEGF or EGFR inhibitors) or radiotherapy were permitted until 4 weeks before study start. In the phaseIIa MTD expansion, patients with non small cell lung cancer (any histology) were divided into two cohorts: cohort A, erlotinibna ¡§ve; and cohort B, erlotinibresistant (those with disease progression while taking erlotinib within the previous 3 months) |
| Biomarker: | EGFR mutations ; |
| Biomark Analysis: | At MTD, BMS690514 modulated pharmacodynamic biomarkers associated with inhibition of VEGFR and EGFRsignalling pathways. |
| Control Group Info: | Inphase I: patients with advanced solid tumours received BMS690514. Inphase Iia: erlotinibna ve (cohort A) or erlotinibresistant (cohort B) patients with advanced non small cell lung cancer (non small cell lung cancer) received BMS690514 |
| Treatment Info: | Phase I was a standard 3 + 3 dose-escalation study enrolling patients in cohorts of P3. The starting dose was 40 mg oncedaily, with planned dose escalations in ubsequent cohorts to 80, 160, 300, 500, 700 and 900 mg oncedaily; intrasubject dose escalation was not permitted.phase IIa included erlotinibna ¡§ve and erlotinib resistant patients with non small cell lung cancer who were dosed at the MTD. |
| Primary End Point: | MTD, DLTs, tumor response and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 90 |
| Trial Results |
| DLT_MTD: | Inphase I (n=28), the MTD was determined to be 200mg daily |
| Objective Response Rate: | Disease control (more than and equal to 4months) and objective response rates, respectively, were 43.3% and 3.3% (cohort A) and 22.6% and 3.2% (cohort B). Six of 21 (29%) non small cell lung cancer patients with wildtype EGFR achieved disease control versus seven of 10 (70%) patients with EGFR mutations (including T790M). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 108 and 50 days, respectively |
| Adverse Event(agent arm): | Inphase IIa (n = 62), the most frequent treatmentrelated adverse events were diarrhoea and acneiform rash. Adverse events that led to >1 discontinuation were diarrhoea (n = 4; 4%) and rash (n = 2; 2%). |
| Conclusions: | Thisphase IIIa study suggests that BMS690514 has manageable safety profile and antitumour activity in patients with non small cell lung cancer at 200mgd, including those with EGFR mutations conferring resistance to erlotinib. |