CHICAGO, Ill. -- American Society of Clinical Oncology (ASCO) 2019 kicked off its annual conference Friday at the Chicago McCormick Place with a clinical science symposium titled "EGFR and ROS1: Targeting Resistance."

Notably, two drug candidates presented at the symposium this year have special ties to Korea in that both drug candidate substances expanded into global trials after confirming the possibility of its success in phase 1 clinical trial conducted in Korea.

Professor Cho Byoung-chul of Yonsei Cancer Center presents the data for the TRIDENT 1 study, during the ASCO 2019 clinical science symposium at the McCormick Place in Chicago, Ill., on Friday.

Professor Cho Byoung-chul of Yonsei Cancer Center in South Korea, one of the pioneering researchers in the country’s oncology community, presented his data highlighting the safety and preliminary clinical activity of Repotrectinib in patients with advanced ROS1 fusion-positive non-small cell lung cancer.

Professor Eric B. Haura from the department of thoracic oncology at the Moffitt Cancer Center and Research Institute in the U.S. also caught the eyes of participants with a bispecific JNJ-372 as a way to overcome resistance for Osimertinib (Product: Tagrisso). JNJ-372 is a drug that is also attracting attention because of its synergy with Lazertinib, a third-generation EGFR targeting drug candidate developed by Yuhan.

"The fact that the two candidates launched its clinical trials in Korea, and a Korean professor who participated in related clinical trial was invited to the first session of the ASCO 2019 means that our country's clinical competence is recognized globally," a Korean doctor attending ASCO 2019 said to Korea Biomedical Review, asking to remain anonymous.

The Repotrectinib phase 1 clinical data, also known as TRIDENT-1 study, introduced by Professor Cho, was evaluated as a powerful alternative for overcoming Crizotinib resistance.
Repotrectinib is an investigational next-generation tyrosine kinase inhibitor (TKI) designed to effectively target ROS1 and TRK A/B/C and systemically overcome resistant mutations that invariably result following treatment with other TKIs.

The objective response rate (ORR) of the G2032R mutation, which is the most common resistance in crizotinib, is 40 percent. The trial showed that the ORR of patients receiving once a day regimen of Repotrectinib 160 mg was 67 percent.

Also, the treatment had an ORR of 82 percent among patients without prior TKI therapy, which had the highest ORR among ROS1-positive non-small cell lung cancer treatments, including Crizotinib. The ORR for patients with brain metastases was also 100 percent. The ORR of Repotrectinib in patients with brain metastases was 75 percent among G2032R mutation.

“With additional follow up and new patients enrolled in the TRIDENT-1 study, repotrectinib continues to demonstrate promising efficacy and a safety profile consistent with a potential best-in-class ROS1 therapy for patients with advanced non-small cell lung cancer,” Professor Cho said.

The ongoing Phase 1 data remain encouraging in both TKI-naïve patients with intracranial disease and patients pretreated with crizotinib -- including those with difficult to treat solvent front mutations -- where there are currently very few therapeutic options, he added.

Repotrectinib is also a potent counterforce against G2032R, the most common mutation that appears after Crizotinib treatment and is effective in patients with TRAK-C and ALK mutations, Cho noted.

Regarding the comment that identified the most effective treatment sequence and appropriate dose, Professor Cho said that is effective to use Repotrectinib as a first-line treatment, which was the only substance that had an ORR over 80 percent for patients with no TKI treatment experience.

The Korean professor also stressed that the number of patients that participated in the TRIDENT-1 study was not small in size as the clinical trials that led to the approval of crizotinib, the only indication for ROS1-positive NSCLC, or Entrectinib, which is expected to receive sales approval

Professor Eric B. Haura’s presentation on JNJ-372, developed by Johnson & Johnson, a bi-specific antibody that simultaneously attacks EGFR and cMet, the treatment has high expectations of becoming an effective alternative treatment as it has shown 28 percent ORR for third-generation TKI resistance and 30 percent ORR for exon20ins patients.

The treatment has also been receiving attention as part of combination therapy with other drugs such as other EGFR TKI or immunotherapy. Currently, JNJ-372 is trying to use combination therapy with a variety of medications, including Lazertinib.

In particular, Lazertinib has been evaluated as having a strong effect on patients with brain cancer as it was able to cross the blood-brain barrier that JNJ-372 had failed to cross. Such synergy between the two treatments has hyped up attention for the combination treatment.

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