FDA Grants Fast Track Designation to TH1902 in SORT1+ Recurrent, Advanced Solid Tumors

The FDA has granted Fast Track designation (FTD) to the investigational peptide drug conjugate TH1902 for the treatment of patients with sortilin positive recurrent advanced solid tumors that are refractory to standard therapy, announced Theratechnologies Inc.¹

“Receiving fast track designation for TH1902 at this early stage of development is a significant recognition for our SORT1+ Technology and further supports the future development of TH1902. The designation, which applies to all solid tumors expressing sortilin, also highlights the broad applicability and immense medical need for innovative, targeted, and potentially more effective and better-tolerated therapies for cancer,” said Christian Marsolais, PhD, senior vice president and chief medical officer, Theratechnologies, in a statement.

Recently, the FDA also issued a “Study May Proceed” letter for the phase 1 clinical trial of TH1902 in patients with advanced solid tumors refractory to available anti-cancer therapies (NCT04706962). The first-in-human, open-label study will follow a dose-escalation design in 2 parts. In part 1, investigators will evaluate the incidence of adverse events and the maximum tolerated dose (MTD) of TH1902, as coprimary end points. The secondary end points that will be explored in part 1 include efficacy and plasma concentration. In part 2, the primary end point is to find the recommended phase 2 dose of TH1902.

Roughly 25 patients will be enrolled in part 1, and 40 additional patients will be enrolled after the MTD is determined.

The study is actively recruiting patients who are 18 years of age or older who had histologically or cytologically confirmed diagnostic of metastatic cancer or advanced-stage disease, and measurable disease per RECIST v1.1 criteria. Per the study enrollment criteria, patients are required to have an ECOG performance status of 0 to 1 and a life expectancy of at least 3 months to be included in part 1 of the study.

To be eligible for part 2 of the study, patients are required to have histologically or cytologically confirmed triple-negative breast cancer (TNBC), gynecologic cancers, colorectal cancer, or pancreatic cancer that does not derive efficacy from standard therapy. These cancers were chosen for their sortilin receptor (SORT1) expression, which is found in 40% to 90% of cases.

The study will be initiated in the second quarter of 2021 and Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, will be the lead principal investigator.

The rationale for the launch of this phase 1 study derives from early research in TNBC and ovarian cancer, which showed that peptide-drug conjugates that target SORT1 have the ability to inhibit vasculogenic mimicry (VM), a formation that contributes to chemoresistance and tumor progression.²

In the TNBC and ovarian tumor cells that SORT1 was detected in, the use of peptide-drug conjugates led to a 50% (IC50) decrease in the formation of new 3D tubular structures at low nM concentrations (5-10 nM). Notably, in an in vitro model of ovarian cancer, a doxorubicin-peptide conjugate, TH1904, which is also developed by Theratechnologies Inc, destroyed the 3D-structure formation. In contrast, unconjugated doxorubicin or liposomal doxorubicin did not impact structure formation. It was also notable that the use of TH1902 in these in vitro TNBC models led to potent activity against VM formulation of 30 pM versus 0.5 nM for docetaxel.

With an FTD, Theratechnologies’ will be granted more frequent meetings and written communication with the FDA to discuss the development of TH1902. This designation also makes TH1902 eligible for Priority Review designation and Accelerated Approval, given the clinical trial meets the relevant criteria. The agent will also be eligible for Rolling Review, meaning that sections of an application for approval submitted to the FDA can be submitted before the entire application is complete.¹

_References:

_{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 February 5, 2021. https://bit.ly/36Om3Dc}

_{Currie JC, Demeule M, Larocque A, et al. Sortilin receptor-mediated novel cancer therapy: A targeted approach to inhibit vasculogenic mimicry in ovarian and breast cancers. Clin Can Res. 2020;80(suppl 16):685. doi:10.1158/1538-7445.AM2020-685}