A phase 1/2 clinical trial for an investigational RET 1 inhibitor showed positive findings, including tumor regression and general tolerability.
The phase I portion of the trial studying TPX-0046 looked at dosing. According to a release from the manufacturer, the study also looked at objective response and found that the drug had a “generally well-tolerated safety profile. The trial included 21 patients, 11 with medullary thyroid carcinoma, and 10 with non-small cell lung cancer, including 3 with RET-altered TKI-naïve NSCLC, all of whom had been previously treated with platinum-based chemotherapy and immunotherapy.
All 16 TKI-pretreated patients had been treated with a selective RET TKI, and 9 were treated with more than one TKI before the trial. Overall, 91% had a baseline ECOG performance score of 1, with nearly half having received three or more prior therapies.
The trial included five RET TKI-naïve patients, of which 4 showed tumor regressions ranging from -3% to -42%, including 2 who achieved partial responses with a duration of 5.6 and 5.8+ months on the 30 mg dose. Three of the patients with regressions stayed on treatment while awaiting their next scan. Three out of nine TKI-pretreated patients achieved tumor regressions ranging from -17% to -44%. Out of 14 evaluable patients, half remained on treatment with durations from 5.1 weeks to 51+ weeks.
“RET-driven cancers affect nearly 10,000 patients annually in the US and EU, and patients who progress following treatment with a selective RET inhibitor remain particularly underserved,” said Alexander Drilon, MD, chief, Early Drug Development Service, at Memorial Sloan Kettering Cancer Center. “While we continue to evaluate TPX-0046, the initial preliminary data are encouraging, with a generally tolerable safety profile and early signals of activity.”
As of the March 10 cut-off date, 21 patients with RET-altered NSCLC or MTC were treated with the drug at doses ranging from 10mg once daily to 30mg once daily. The most frequent treatment-emergent adverse events were grade 1 or 2 dizziness. The maximum tolerated dose had not been determined as of the cutoff date “with 1 dose-limiting toxicity of treatment-related Grade 2 gait disturbance at the 30 mg dose,” according to the release.
The most common treatment-emergent adverse events reported in more than 20% of patients included dizziness, fatigue, decreased appetite, and dry mouth. The release noted “infrequent” dose reductions or discontinuations due to the adverse events.
Mohammad Hirmand, MD, executive vice president and chief medical officer of Turning Point Therapeutics, said based on the data so far, they plan to modify the study to include dose expansion at additional sites.