• Everolimus (Afinitor) has been approved by the European Commission for treatment of unresectable or metastatic, well-differentiated (grade 1 or grade 2) nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin in adults with progressive disease. Everolimus is the first approved therapy in all European Union (EU) member states, plus Iceland and Norway, for this type of lung NET, and one of few treatment options available for this type of GI NET.
The EU approval of everolimus was based on data from the RADIANT-4 trial evaluating everolimus versus a placebo in patients with advanced, progressive, welldifferentiated nonfunctional NET of GI or lung origin. Everolimus was previously approved (February 2016) by the FDA for treatment of adults with progressive, well-differentiated nonfunctional NET of GI or lung origin that are unresectable, locally advanced or metastatic.
“The approval of everolimus offers a treatment option to patients with NET of GI or lung origin in the EU for whom evidence-based effective systemic therapies were previously lacking,” says J.C. Yao, MD, corresponding author of the RADIANT-4 trial.
• LOXO-101, a selective inhibitor of tropomyosin receptor kinase (TRK), was granted Breakthrough Therapy Designation by the US FDA “for the treatment of unresectable or metastatic solid tumors with neurotrophic tyrosine receptor kinase (NTRK)- fusion proteins in adult and pediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments.”
Investigators enrolled 41 patients with tumors refractory to other available therapies. No patients without a fusion showed activity. However, in those patients with NTRK fusions present, 83% had a response. In patients with TRK mutation or amplification, 60% were able to achieve disease control. While the patient number was small and the findings early, study data provide the rationale for continued exploration of LOXO-101 in patients with NTRK gene fusions.
A phase 2 basket trial (NCT02576431) is underway to evaluate LOXO-101 in adults with cancer whose tumors harbor NTRK fusions.
• Olmutinib (BI 1482694/HM61713), which was granted Breakthrough Therapy Designation by the US FDA in December 2015, has recently been approved in South Korea for treatment of locally advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer previously treated with an EGFR tyrosine kinase inhibitor (TKI). A novel third-generation oral agent, olmutinib is an EGFR mutation-specific TKI.
Olmutinib is currently in accelerated development through the ELUXA clinical trial program, with the goal of submitting data and evidence to the FDA and the European Medicines Agency in 2016. The approval of olmutinib represents a first for South Korean regulatory authorities.
“The approval of olmutinib is a step forward for patients with lung cancer in South Korea. This is a needed new treatment option for the majority of EGFR mutation-positive lung cancer patients whose disease has become resistant to firstline TKI therapy,” comments Professor Keunchil Park, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
• Seribantumab (MM-121; Merrimack Pharmaceuticals) has received FDA Fast Track designation for development to treat patients with heregulin-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed following immunotherapy.
Seribantumab is designed to block heregulin-driven signaling and enhance the anti-tumor effect of chemotherapy in cancer, including NSCLC. The global SHERLOC trial is evaluating seribantumab in combination with docetaxel or pemetrexed in heregulin-positive patients with NSCLC. The data from this study will be used to support a biologics license application to the FDA.
“We are pleased that the FDA recognizes the importance of investigating a novel biomarker-directed agent such as seribantumab,” says Akos Czibere, MD, Merrimack Pharmaceuticals. “Heregulin-positive cancer cells are characterized by their ability to escape the effects of a broad range of cancer therapies and potentially contribute to accelerated disease progression.… This is important because we find that more than 50% of patients with NSCLC are heregulin-positive.”
