Phase 1
Phase 2
Phase 3

Patient enrollment ongoing

Overview

Sym004 induces rapid internalization and degradation of the EGFR that leads to down-modulation of EGFR and subsequent inhibition of cancer cell growth. The inhibition of EGFR with two antibodies contained in Sym004 results in a mechanism of action that is distinct from the more limited actions of single anti-EGFR antibodies.

In preclinical models of GBM in which EGFR amplification is present, Sym004 demonstrated promising efficacy. In general, up to 50 percent of GBM patients have amplified EGFR. By removing the EGFR receptors from the surface of the tumor cell and thus preventing tumor growth, Sym004 may provide a new treatment option for GBM patients.

Target
EGFR
Trial
Phase 2a ongoing
Patients
Single center trial in up to 92 patients

Ongoing trial design and results

The ongoing trial is designed as a single center trial in up to 92 patients with EGFR-amplified GBM. Patients are randomized into one of two cohorts: non-Avastin® (bevacizumab) failures and Avastin® (bevacizumab) failures.

End-points
The primary objective of the trial is to assess the efficacy of Sym004 in terms of six-month progression free survival (PFS). Secondary objectives of the trial include to determine overall survival, safety, and response rates.
Status
Based on tolerability of a 18 mg/kg biweekly dose in 27 patients, the dose has been increased to 24 mg/kg biweekly and enrollment at this higher dose level is ongoing.

Glioblastoma market facts

Prevalence
In 2017, an estimated 56,000 treatable patients with GBM were living in the United States and the European Union. With an estimated annual growth rate of 1.5 percent this will have grown to 63,000 in 2024.

Survival
GBM is a highly aggressive malignant primary brain cancer. Median overall survival is under 15 months.

Value
The 2017 market for GBM therapies is estimated at DKK 6.7 billion and is expected to grow 17.5% annually until 2024 (CAGR).

Current treatment
GBM is a relatively rare disease and treatment options are limited. Temozolomide, an alkylating agent, is the current standard of care in combination with surgical resection and radiation therapy. Recurrent GBM has an initial response to temozolomide therapy, but patients lose sensitivity to the drug over time.

In 2009, Avastin® was also approved for treatment of metastatic/refractory GBM based on preliminary clinical studies. However, subsequent studies showed no overall survival benefits of Avastin treatment in recurrent GBM. Avastin has nonetheless achieved full approval and remains the current standard of care.

The unmet medical needs for this disease are thus extremely high, making GBM an attractive market opportunity for a more effective therapy that provides survival benefit.

 

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