Conference Coverage

Repotrectinib highly active in ROS1-positive lung cancer



– The oral tyrosine kinase inhibitor (TKI) repotrectinib is safe and has demonstrated encouraging activity in patients with advanced ROS1 fusion-positive non-small cell lung cancer, early results of a phase 1/2 study show.

Objective response rates of 82% in 11 TKI-naive patients and 39% in 22 TKI-pretreated patients were seen after treatment with repotrectinib, a next-generation inhibitor of ROS1/TRK/ALK with a 90-fold greater potency for ROS1 versus crizotinib, according to an investigator in the study.

“The TRIDENT-1 study supports repotrectinib as a potential best-in-class ROS1 agent in advanced non–small cell lung cancer,” said investigator ByoungChul Cho, MD, PhD, of Yonsei Cancer Center in Seoul, South Korea, in a podium presentation at the annual meeting of the American Society of Clinical Oncology.

For the 11 TKI-naive patients, no median duration of response had yet been reached over a median follow-up duration of nearly 17 months, with individual response durations that ranged from 10.9 to 17.7 or more months in the 5 of 9 patients remaining in response, Dr. Cho reported.

“This is exciting, because this is the most promising data presented so far with ROS1 TKI in TKI-naive patient population,” Dr. Cho said.

Repotrectinib also showed a potential to overcome TKI resistance mutations, notably G2032R, which is the most common ROS1 resistance mutation after crizotinib treatment.

All five patients with ROS1 G2032R mutation experienced tumor regression, with a confirmed response rate of 40%, Dr. Cho said.

The TKI was relatively well tolerated with four dose-limiting toxicity events including grade 2-3 dizziness in three cases and grade 3 dyspnea and hypoxia in one case.

Of four grade 5 treatment-emergent adverse events, only one case was possibly related to the treatment, Dr. Cho said.

Based on this tolerability and preliminary activity, the pivotal phase 2 portion of TRIDENT-1 is set to begin in the second half of 2019.

Benjamin Besse, MD, PhD, of Paris-Sud University, Orsay, and Institut Gustave Roussy said these preliminary results were very encouraging.

“If we look at the global picture, repotrectinib is probably today the most potent TKI against ROS1,” Dr. Besse said in a podium discussion of the results. “We don’t know yet if this will translate in an improved progression-free survival.”

Close follow-up of adverse events are warranted in further investigations because of the potency of the drug, he added.

Turning Point Therapeutics sponsored the study. Dr. Cho reported disclosures related to TheraCanVac, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, Janssen, Mogam Institute, MSD, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan.

SOURCE: Cho BC et al. ASCO 2019, Abstract 9011.

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