Phase 1 Trial Pauses Enrollment for Evaluation of TH1902 in Sortilin-Expressing Cancers

Christian Marsolais, PhD

Enrollment has been paused for a phase 1 trial (NCT04706962) investigating the peptide-drug conjugate (PDC) TH1902 for the treatment of patients with sortilin-expressing cancers, according to an announcement from Theratechnologies Inc.¹

The trial was paused voluntarily by Theratechnologies following consultation with study investigators, and the pause will allow the company to revisit the study design. The company said efficacy and safety results reported to date were not convincing enough to pursue continued enrollment. Reported adverse effects consisted mainly of neuropathy and eye toxicity.

The company plans to amend the protocol to modify the dosage regimen with lower doses at more frequent intervals.

“While we are disappointed with these developments, we remain committed to advancing our SORT1+ Technology platform and will continue investigating its potential in the treatment of advanced cancers,” Christian Marsolais, PhD, senior vice president and chief medical officer of Theratechnologies, stated in a press release.

The SORT1+ Technology is being developed by Theratechnologies for cancer drug development targeting SORT1 receptors, which play a significant role in protein internalization, sorting, and trafficking. SORT1 is highly expressed in cancer cells compared with healthy tissue, and expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival.

TH1902 is the lead PDC being developed by Theratechnologies. The peptide is linked to docetaxel. In February 2021, the FDA granted fast track designation to TH1902 for the treatment of patients with sortilin-expressing cancers.²

The open-label, first-in-human phase 1 study of TH1902 is investigating TH1902 in patients with solid tumors.³ The trial consists of a dose-escalation phase (part 1), which includes patients with recurrent advanced solid tumors that have relapsed or are refractory to standard chemotherapy, surgery, radiation therapy, and for which no known effective therapies exist.

The dose-expansion phase (part 2) is investigating TH1902 in selected patient populations with recurrent advanced triple-negative breast cancer, hormone receptor–positive breast cancer, epithelial ovarian cancer, endometrial cancer, cutaneous melanoma, thyroid cancer, small cell lung cancer, prostate cancer, and other cancers known to express SORT1 that are refractory to standard therapy.

Key inclusion criteria include patients who are at least 18 years of age with measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months. Exclusion criteria include chemotherapy, biologic therapy, immunotherapy, radiotherapy (except palliative radiation delivered to <20% of bone marrow), or investigational agents within 4 weeks of the first study dose; hypersensitivity to taxanes, including docetaxel, or to any excipients in TH1902; severe toxicity with previous taxane treatment; or leptomeningeal disease, spinal cord compression, or active brain metastases.

In part 1 of the trial, which was designed to evaluate the safety, pharmacokinetics, maximum tolerated dose (MTD), and preliminary antitumor activity of TH1902, the agent was administered once every 3 weeks in patients with advanced solid tumors refractory to available anticancer therapies.² Once the MTD is determined for part 2, the trial planned to enroll 40 additional patients with endometrial, ovarian, colorectal, pancreatic, and triple-negative breast cancers to evaluate the potential antitumor activity of TH1902.

Primary end points of the trial included safety and tolerability, plus establishing the MTD and recommended phase 2 dose. Secondary end points include efficacy and plasma concentration.

References

1. Theratechnologies announces update from ongoing TH1902 study. News release. Theratechnologies Inc. December 1, 2022. Accessed December 5, 2022. https://bit.ly/3h1hGgd
2. Theratechnologies’ lead peptide drug conjugate TH1902 receives FDA fast track designation for the treatment of sortilin-expressing cancers. News release. Theratechnologies Inc. February 4, 2021. Accessed December 5, 2022. https://bit.ly/3umggjD
3. TH1902 in patients with advanced solid tumors. ClinicalTrials.gov. Updated June 30, 2022. Accessed December 5, 2022. https://clinicaltrials.gov/ct2/show/NCT04706962