Safety and pharmacokinetics (PK) of AMG 706, panitumumab, and carboplatin/paclitaxel (CP) for the treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)

Abstract

7119 Introduction: AMG 706 is an investigational, oral, multi-kinase inhibitor with both antiangiogenic and direct antitumor activity targeting VEGF, PDGF, and Kit receptors. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFr), has shown antitumor activity and acceptable safety in pts with solid tumors. Methods: This is an ongoing, multicenter, dose finding, phase 1b study of AMG 706 with panitumumab and CP in pts with advanced NSCLC. Primary objectives were to assess the safety and PK of AMG 706; secondary objectives included drug exposure and objective response rates. Pts had stage IIIB/IV NSCLC, ECOG score of 0–1, no symptomatic or untreated CNS metastases, and no prior chemotherapy for NSCLC (segments A&C) or ≤ 1 regimen for NSCLC (segment B). AMG 706 was given orally either QD (50 mg or 125 mg) or BID (75 mg) with CP Q3W (P:200 mg/m2; C: AUC = 6 mg/mL · min; Segment A), with panitumumab (9.0 mg/kg Q3W; Segment B), or with CP+ panitumumab (Segment C). AMG 706 was dosed continuously in 21-day cycles (days 3–21 in cycle 1; days 1–21 in cycle 2 and beyond); pts were sequentially enrolled into escalating AMG 706 dose cohorts. Results: As of 9/05, 22 pts were enrolled (10 in A, 12 in B) into AMG 706 dose cohorts of 50 mg and 125 mg QD. In A and B, respectively, 7 and 6 pts were men; median (range) age was 60.5 (60, 74) and 60.5 (55.7, 71.0). One pt in the 125 mg QD cohort in Segment B had grade (gr) 5 pneumonia. Treatment-related adverse events occurring in >5% of all patients are summarized ( table ). Preliminary data showed that AMG 706 PK profiles were similar when administered with CP either 30 min or 48 hrs apart. At 50 mg QD, there was no effect of AMG 706 on the PK of P. Conclusions: Preliminary data indicate that AMG 706 can be combined safely with CP or panitumumab in pts with advanced NSCLC and that there is no effect on the PK of AMG 706 or P. Updated data will be presented. [Table: see text] [Table: see text]