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OncoMed completes patient enrollment in phase 2 trial of tarextumab in SCLC

OncoMed Pharmaceuticals has completed patient enrollment in the Phase 2 "PINNACLE" clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) for the treatment of small cell lung cancer (SCLC).

The PINNACLE study enrolled 145 patients with extensive-stage SCLC who had not received prior treatment.  Topline data from the Phase 2 trial are expected to be reported at the end of 2016 or in early 2017.

Jakob Dupont, M.D., Chief Medical Officer of OncoMed, said: "Our PINNACLE Phase 2 trial accrued patients more quickly than anticipated and we would like to thank the patients, their families, caregivers and the participating investigators and study site personnel for their participation.  Small cell lung cancer is a difficult to treat cancer and unfortunately most patients survive a year or less.  New and improved treatment options are needed for these patients. 

"In a Phase 1b dose-escalating trial of tarextumab in small cell lung cancer we observed that patients who received standard-of-care chemotherapy in combination with tarextumab near or at the selected Phase 2 dose appeared to have deeper anti-tumor responses and improved survival outcomes, particularly in tumors that were high in certain Notch pathway genes.  We look forward to seeing if these observations are maintained in our Phase 2 trial and anticipate reporting data from PINNACLE at the end of 2016 or in early 2017."

Patients enrolled in the PINNACLE trial were randomized into two study arms and received either 15mg/kg of tarextumab every three weeks in combination with six cycles of etoposide and platinum therapy followed by tarextumab maintenance to progression or six cycles of standard chemotherapy and a placebo. 

The primary endpoint of the trial is progression-free survival.  Secondary endpoints include overall survival and overall response rate, pharmacokinetics, safety and biomarker analyses.  Overall survival, progression-free survival and overall response rates will be assessed against elevated tumor expression of certain Notch pathway genes. 

The protocol for the Phase 2 trial was amended in May 2016 to enable the assessment of efficacy outcomes using Notch pathway genes Hes1, Hes6, Hey1 and Hey2 as a secondary endpoint. 

The PINNACLE trial was conducted at 36 sites in the United States.  Enrollment in the randomized, double-blinded, multi-center clinical study began in December 2014 and was completed three months ahead of schedule. 

In the Phase 1b trial, all 26 patients evaluable for tumor response saw a reduction in target lesion size as measured by RECIST criteria, with an overall response rate of 77% and a 100% clinical benefit rate. 

Subjects receiving doses of tarextumab at or above 12 mg/kg plus chemotherapy achieved a median progression-free survival of 5.2 months and a median overall survival of 16 months.  Results from OncoMed's Phase 1b trial of tarextumab were most recently presented at the 2016 ASCO Annual Meeting.

About Small Cell Lung Cancer

According to the American Cancer Society, lung cancer (both small cell and non-small cell) is the second most common cancer in men and women and is by far the leading cause of cancer death. 

Small cell lung cancer is expected to make up about 10%-15% of the 224,390 newly diagnosed lung cancer cases and the 158,080 deaths estimated to occur in the U.S. in 20161.  SCLC tends to grow and spread quickly, and is typically not discovered until it has metastasized to other parts of the body (extensive stage). 

The current standard of care in treating small cell lung cancer is the chemotherapeutic etoposide in combination with either cisplatin or caboplatin.  In spite of a high sensitivity to chemotherapy and remission rates of up to 80% following initial treatment, the median overall survival is less than one year for patients with extensive stage disease.

About Tarextumab (anti-Notch2/3, OMP-59R5)

Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors.  Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment.  

Tarextumab is being studied in the "PINNACLE" study (A Phase 1b/2 Study of OMP-59R5 in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer).  Tarextumab is part of OncoMed's collaboration with GlaxoSmithKline (GSK).  GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.