Repotrectinib for ROS1-Positive NSCLC Examined in Phase I/II TRIDENT-1 Trial
Early trials of the targeted oral drug repotrectinib discovered that it may help treat patients with a certain type of non–small cell lung cancer (NSCLC), according to a new study published by Cho et al in the European Journal of Cancer. The results of the TRIDENT-1 trial—presented at the 34th European Organisation for Research and Treatment of Cancer (EORTC)–National Cancer Institute (NCI)–American Association for Cancer Research (AACR) Symposium on Molecular Targets and Cancer Therapeutics (Abstract 2LBA)—suggested that repotrectinib could be effective for treating ROS1-positive NSCLC.
This type of NSCLC accounts for 1% to 2% of lung cancer cases and is more often found in younger people, women, and nonsmokers.
“Repotrectinib is a new type of tyrosine kinase inhibitor drug … that works by blocking the signals that tell cancer cells to grow and divide. Other [tyrosine kinase inhibitors] are already in use for treating NSCLC; however, cancers can become resistant to these treatments. In particular, the cancer can spread to the brain, where it is especially difficult to treat,” said first study author Byoung Chul Cho, MD, PhD, Professor of Medical Oncology at the Yonsei Cancer Center at the Yonsei University College of Medicine.
Byoung Chul Cho, MD, PhD
TRIDENT-1 Methods and Results
TRIDENT-1 was a phase I/II clinical trial primarily run to test the safety and efficacy of repotrectinib. Trial participants were given repotrectinib once daily and could continue the treatment as long as they could tolerate it or until their conditions deteriorated.
The trial included more than 400 people with ROS1-positive NSCLC who were treated at one of 150 hospitals around the world. Some patients with NSCLC had never been treated with a ROS1 tyrosine kinase inhibitor; some had previously been treated with one ROS1 tyrosine kinase inhibitor; some had been treated with a ROS1 tyrosine kinase inhibitor and platinum-based chemotherapy; and some had been treated with two different ROS1 tyrosine kinase inhibitors.
Researchers were able to assess the safety of the treatment in 444 patients and the efficacy of the treatment in 171 patients. Among those who had not previously been treated with a ROS1 tyrosine kinase inhibitor, researchers found an objective response rate of 79%. In patients previously treated with a ROS1 tyrosine kinase inhibitor, in patients treated with a ROS1 tyrosine kinase inhibitor and chemotherapy, and in patients treated with two different ROS1 tyrosine kinase inhibitors, the objective response rates were 38%, 42%, and 28%, respectively.
Among the small number of patients who had measurable brain tumors, the intracranial objective response rates were 88% in patients not previously treated with a ROS1 tyrosine kinase inhibitor, 42% in those treated with one prior ROS1 tyrosine kinase inhibitor, 50% in those treated with one prior ROS1 tyrosine kinase inhibitor and chemotherapy, and 0% in those treated with two prior ROS1 tyrosine kinase inhibitors.
Side effects of the treatment included dizziness, changes to the sense of taste, constipation, and anemia.
“These results suggest that repotrectinib is having an effect on tumors in patients with this type of lung cancer, including on tumors that have spread to the brain. There are signs that the drug could help both patients who have not been treated with a [ROS1 tyrosine kinase inhibitor] and those who have received previous treatment, suggesting that repotrectinib could have effects even when cancers become resistant to other treatments. I believe that further testing and development of this drug could help more patients with ROS1-positive NSCLC,” concluded Dr. Cho.
“Lung cancer is the leading cause of cancer death worldwide, and we urgently need new treatments, especially for patients whose cancer has spread to other part of the body, such as the brain. The results of this phase I/II clinical trial suggest that repotrectinib may bring benefits to patients with a particular type of lung cancer,” said Ruth Plummer, MD, PhD, Professor of Experimental Cancer Medicine at Newcastle University and Chair of the 34th EORTC–NCI–AACR Symposium on Molecular Targets and Cancer Therapeutics, who was not involved in the study.
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