Ignyta has found positive results from its Phase 1 clinical trials of entrectinib, its proprietary oral tyrosine kinase inhibitor targeting solid tumours harbouring activating alterations to NTRK1, NTRK2, NTRK3, ROS1 or ALK.
The trials included the ALKA-372-001 study and the STARTRK-1 study, which is claimed to be first of the ‘Studies of Tumour Alterations Responsive to Targeting Receptor Kinases’.
Both trials were designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent entrectinib in patients with solid tumours with the relevant target alterations – TrkA (encoded by NTRK1), ROS1 or ALK for ALKA-372-001 and TrkA/TrkB/TrkC (encoded by NTRK1/2/3), ROS1 or ALK for STARTRK-1.
Ignyta Chairman and CEO Jonathan Lim said: "With respect to efficacy, in the 25 patients in the Phase 1 trials who would meet the eligibility criteria for our Phase 2 clinical trial, we saw tumour regression in 20 patients, or 80%.
"Nineteen out of 24 patients with extracranial solid tumours had a confirmed RECIST response, representing a 79% overall response rate; and one patient with an astrocytoma had evidence of substantial tumour regression by volumetric measurement.
"These responses were observed in patients with each of NTRK, ROS1 and ALK rearrangements, and across six tumour histologies, including complete and/or durable responses in both primary and metastatic tumours of the central nervous system."
The Phase 1 clinical trials included four patients with NTRK1/2/3 gene rearrangements that met the company’s Phase 2 eligibility criteria, including patients with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), salivary gland cancer and astrocytoma.
All four of these patients demonstrated tumour regression (three confirmed responses by RECIST and one by volumetric assessment), while two of these Trk patients remained on study, one of whom had been on study for longer than 12 months.
A total of 14 patients were included in the clinical studies with ROS1 gene rearrangements who met the company’s Phase 2 eligibility criteria, including 13 patients with NSCLC and one patient with malignant melanoma.
Eleven of the 13 patients with NSCLC and the patient with melanoma responded, including two complete responses. The resultant overall response rate for these ROS1 patients was 86%, and the response rate for the subset of patients with NSCLC was 85%.
Eleven of the ROS1 responders remained on study in response, with the longest at 27 months; one ROS1 NSCLC patient has met the criteria for RECIST progression but has remained on study due to clinical benefit.
Phase 1 clinical trials included seven patients with ALK gene rearrangements who met the company’s Phase 2 eligibility criteria, including four patients with NSCLC, one patient with CRC, one patient with renal cell carcinoma (RCC) and one patient with a thoracic tumour of unknown primary.
Two of the four patients with NSCLC, the patient with CRC and the patient with RCC had clinical responses, while another NSCLC patient had stable disease.
The resultant overall response rate for these ALK patients was 57%.
Two of the responders remained on study in response, as did the patient with stable disease.
Lim added: "With respect to safety, based upon a larger dataset of 119 patients, which included 45 patients treated at our Phase 2 dose of 600 mg continuous once daily dosing, we have been able to further substantiate entrectinib’s acceptable safety profile.
"We have 19 patients who have been on study for longer than six months; of those, 11 patients have been on study for more than one year, including three patients for more than two years.
"We believe these data highlight the long-term tolerability and promising anti-tumour activity of entrectinib as we continue to enroll STARTRK-2, our ongoing, potentially registration-enabling Phase 2 clinical trial of entrectinib."