US-based developer of next-generation targeted therapeutics for cancer Xcovery has reported positive results from a Phase I/II trial of X-396, a potent small molecule anaplastic lymphoma kinase (ALK) inhibitor.
The results showed that X-396 is generally well-tolerated and has anti-tumour activity in patients with ALK-positive, non-small cell lung cancer (NSCLC).
Vanderbilt-Ingram Cancer Centre associate professor of Medicine and Clinical Director, Thoracic Oncology Program and lead investigator of this Phase I trial, Leora Horn said: "While still early, X-396 continues to demonstrate activity in treatment-naive ALK-positive non-small cell lung cancer patients as well as those that have progressed on crizotinib, and responses have also been seen in patients with central nervous system (CNS) disease.
"We are continuing to enrol patients in the expansion cohort phase of this trial to learn more about this patient population and inform future studies of X-396."
A total of 41 patients were enrolled with tumour types including NSCLC, head and neck, small cell lung, colorectal and breast cancers, at the time of data cut-off.
The company said that the NSCLC (n=33) patient group included ALK-positive patients (n=23) who were either crizotinib-naïve (n=5) or received prior crizotinib (n=18), as well as ceritinib in two patients.
Among the 17 ALK positive patients evaluable for response, ten patients had a partial response and two had stable disease.
For the five patients with progressive disease, two were at lower doses 50mg and 100mg with acquired resistance to crizotinib, one at 200mg had failed prior crizotinib and chemotherapy, and one 250mg had failed prior crizotinib and ceritinib.
The patient with prior crizotinib and ceritinib had a complete response to X-396 in a retroperitoneal lymph node but progression of bone/CNS metastases.
Xcovery executive vice-president and chief scientific officer Chris Liang said: "These results further validate the clinical benefit of X-396 that we presented earlier this year and our belief that X-396 has the potential to be an effective and well-tolerated oral treatment for ALK-positive, non-small cell lung cancer."
The company is developing X-396 to treat solid tumours where ALK is deregulated.
X-396 has been evaluated in potency and selectivity assays indicating that it is more selective and up to ten times more potent than competitive ALK inhibitors.