Small Cell Lung Cancer

April 24, 2017

OncoMed Pharmaceuticals issued results of a 145-patient, phase II trial of tarextumab (anti-Notch2/3, OMP-59R5) in combination with etoposide plus either cisplatin or carboplatin chemotherapy in previously untreated patients with extensive-stage small cell lung cancer. The double-blind, multicenter trial randomized two study arms that received either 15mg/kg of tarextumab every three weeks in combination with six cycles of etoposide and either cisplatin or carboplatin chemotherapy followed by tarextumab maintenance to progression or six cycles of chemotherapy and a placebo. The median progression-free survival (mPFS) for tarextumab plus chemotherapy was 5.6 months versus 5.5 months for chemotherapy plus placebo (HR=0.969). The median overall survival (mOS) analysis did not show a benefit for tarextumab in combination with chemotherapy (mOS=9.3 months) compared to the chemotherapy plus placebo arm (10.3 months; HR=1.01). Five individual Notch biomarkers (Hes1, Hes6, Hey1, Hey2 and Notch3) failed to identify a definitive subset of patients with a treatment effect on either mPFS or mOS. Overall response rates were 68.5% and 70.8% in the tarextumab and placebo arms respectively. The combination of tarextumab plus chemotherapy was well-tolerated.

September 17, 2012

ImmunoGen released results from a phase II trial of IMGN901, in combination with etoposide and carboplatin, for the treatment of small cell lung cancer (SCLC). This randomized, dose-finding study, NORTH, enrolled 120 patients. Subjects received etoposide 100 mg/m2 on days one through three every 21 days; carboplatin AUC5 or AUC6 on day one every 21 days; and IMGN901 ranging up to 112 mg/m2, administered on days one and eight every 21 days. Results showed that IMGN901 112 mg/m2, carboplatin AUC5 and etoposide 100 mg/m2 was the most effective dose. Of the 33 patients dosed with this regimen, 10 had an objective response and 24 (72.7%) had disease control (objective response or stable disease). IMGN901 was well tolerated. The most frequent adverse event was low grade peripheral neuropathy.

October 22, 2007

Threshold issued negative results from a phase II trial of glufosfamide for the treatment of small cell lung cancer. This open-label trial enrolled 50 subjects with recurrent sensitive small cell lung cancer in the US, Ukraine and Russia. The subjects received 5000 mg/m2 of glufosfamide every three weeks for up to six cycles. Tumor response was evaluated at baseline and every six weeks using RECIST criteria. During a planned interim analysis, it was determined that the primary endpoint, objective response rate was not going to be achieved. Based on the results Threshold has stopped enrollment in this clinical trial.

April 30, 2007

Amgen released negative results from a phase III trial of Aranesp for the treatment of small cell lung cancer (sclc). This randomized, double-blind, placebo-controlled trial, dubbed "145 study", enrolled 600 subjects with sclc receiving platinum-containing chemotherapy. Subjects were randomized 1:1 to receive Aranesp 300 mcg or placebo every week for the first 4 weeks, followed by once every three week dosing (commencing on week 5) for the remainder of the 24-week treatment period. Results demonstrated no statistically significant difference in overall survival for Aranesp compared to placebo (Hazard Ratio (HR): 0.93, 95% CI: 0.78 to 1.11) or investigator determined progression-free survival (HR: 1.02, 95% CI: 0.86 to 1.21). However a co-primary endpoint, a significant change in hemoglobin concentration from baseline in favor of Aranesp, was met. Additionally, Aranesp-treated subjects also experienced a significantly lower risk of blood transfusions (HR: 0.40, 95% CI: 0.29 to 0.55). Amgen plans to further evaluate the data in order t o determine a future course of action.