Ignyta’s candidate product entrectinib has shown promise as a treatment for several cancer types including melanoma, according to results of two Phase 1 clinical trials.
Treatment with entrectinib was well-tolerated and induced cancer improvement as early as one month after the first treatment, which was sustained for up to 2.5 years in patients with non-small cell lung cancer (NSCLC), colorectal cancer, mammary analog secretory carcinoma (MASC), melanoma and renal cell carcinoma.
Entrectinib is an oral tyrosine kinase (TRK) inhibitor that blocks the proteins TRKA/B/C, ROS1 and ALK, which are all involved in the pathology of certain cancer types.
The study, “Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1),” appeared in the journal Cancer Discovery.
The two Phase 1 studies (ALKA-372-001 and STARTRK-1, NCT02097810) investigated the efficacy and safety of once-daily oral entrectinib (600 mg) in a group of patients with advanced or metastatic solid tumors carrying genetic deficits in the NTRK1/2/3, ROS1 or ALK genes, and who had never been treated with tyrosine kinase inhibitors before. Patients received entrectinib for 28 days.
Results showed that 63 percent of patients with primary or metastatic disease involving the brain responded to the therapy. In patients with NTRK defects, the longest duration of response was ongoing at about 15 months. The median duration of response was 17.4 months and 7.4 months for patients with cancer marked by ROS1 defects, and 7.4 months for those with cancer marked by ALK defects.
Three patients with NTRK1/2/3-caused tumors (NSCLC, MASC and colorectal cancer) achieved complete cancer response, with complete disappearance of brain metastases in the patient with NSCLC. One patient with NTRK1-caused brain cancer achieved 60 percent reduction in tumor burden. Among the 14 patients with ROS1-caused solid tumors, including one melanoma patient and 13 NSCLC patients, the overall response rate was 86 percent, with two complete responses. In seven ALK-caused solid tumors (NSCLC, renal cell carcinoma and colorectal cancer), entrectinib provided a 57 percent response.
Entrectinib treatment was well-tolerated and safe, with mostly mild to moderate side effects, all of which were reversible with dose interruption or modification. Common side effects included fatigue and weakness, loss of taste, skin itching, nausea and muscular pain.
“This … article shows entrectinib responses to be both rapid and durable in patients with advanced solid tumors across multiple [cancer types] and each of the molecular targets of interest, including in multiple patients with metastatic [brain] disease,” Igynta CEO Jonathan Lim, MD, said in a news release.
“These studies show promising potential for entrectinib in both TRK- and ROS1-driven tumors,” said the study’s author, Alexander Drilon, MD. “The anti-tumor activity seen across cancer types and entrectinib’s ability to treat bulky [brain] disease, particularly important given the propensity for many solid tumors to metastasize to the brain, is extremely encouraging.”
Entrectinib is currently being investigated in a new Phase 2 clinical, the STARTRK-2 study (NCT02568267), with patient enrollment ongoing.
