NEW YORK – Turning Point Therapeutics on Saturday reported on the activity of TPX-0022 in multiple solid tumor types and said it would discuss with the US Food and Drug Administration the use of the data for registrational purposes.
The Phase I clinical trial, dubbed SHIELD-1, is assessing the safety and maximum tolerated dose of TPX-0022, an investigational agent designed to inhibit MET and associated SRC and CSF1R pathways. The preliminary results were presented during a virtual symposium hosted by the European Organization for Research and Treatment of Cancer, the National Cancer Institute, and the American Association for Cancer Research.
The trial has enrolled patients with previously treated advanced or metastatic solid tumors, including non-small cell lung cancer, colorectal cancer, gastroesophageal junction or gastric cancer, and glioblastoma. To be eligible for the trial, patients' tumors need to harbor MET alterations, including exon 14 deletions, amplifications, fusions, or activating kinase mutations, as confirmed by fluorescence in situ hybridization (FISH), quantitative PCR, or next-generation sequencing on tissue or liquid biopsies.
At the symposium on Saturday, researchers presented data on 22 patients treated with TPX-0022, 15 of whom were evaluable for the trial's secondary efficacy endpoints. Of these 15 patients, nine achieved a clinical benefit from the drug — which the investigators defined as a confirmed or unconfirmed partial response, or stable disease — and six patients remained on treatment for a duration of 7.6 weeks to 34 weeks.
All three evaluable patients with gastroesophageal junction cancers responded to the drug. Of the 10 evaluable patients who had not previously received a MET inhibitor, five achieved a partial response. Among the five patients who had received a prior MET inhibitor, the best response was stable disease, and two patients' tumors shrunk by 27 percent and 75 percent.
As for the trial's primary safety and tolerability endpoints, the investigators reported that TPX-0022 was for the most part well-tolerated. The maximum tolerated dose of the agent had not been determined at the time of the data cutoff.
"We are encouraged by the emerging early safety and efficacy data across multiple tumor types, including the high unmet medical need area within MET-amplified gastric cancer where there are no approved targeted therapies," Turning Point's Chief Medical Officer Mohammad Hirmand said in a statement. "MET driven cancers affect a large and growing population of patients who have limited therapeutic options. Based on these early study findings, we look forward to advancing the development of TPX-0022."
Contingent on feedback from the FDA, Turning Point said it hopes to modify the trial into a registrational Phase I/II trial, and launch the Phase II portion in the second half of 2021. Additionally, the company plans to evaluate TPX-0022 in combination with an EGFR inhibitor in a study planned for the second half of 2021.