Oncology Medical News about advanced solid tumors;antitumor activity of AMG 386

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Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors
Journal of Clinical Oncology, 06/25/09

Herbst RS et al. - In a trial to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors, it was determined that wkly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor–axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this pt population.

Methods

Pts in sequential cohorts received wkly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg.

Results

32 pts were enrolled and received AMG 386.
1 occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden possibly related to AMG 386.
Most common toxicities were fatigue and peripheral edema.
Proteinuria (n=11) was observed without clinical sequelae.
Only 4 pts (12%) experienced treatment-related toxicities >grade 1.
A maximum-tolerated dose was not reached.
PK was dose-linear and mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days.
Serum AMG 386 levels appeared to reach steady-state after 4 wkly doses, and there was minimal accumulation.
No anti–AMG 386 neutralizing antibodies were detected.
Reductions in volume transfer constant were observed in 10 pts (13 lesions) 48 hrs to 8 wks after treatment.
1 pt with refractory ovarian cancer achieved a confirmed partial response and withdrew with a partial response after 156 wks of treatment; 4 pts experienced stable disease for at least 16 wks.