Faeth Therapeutics & GOG-F Launch Phase 2 Trial for Sapanisertib-Serabelisib in Endometrial Cancer
Faeth Therapeutics (Faeth), a clinical-stage biotechnology company dedicated to pioneering novel metabolism-based therapeutic strategies, and The GOG Foundation, Inc. (GOG-F), a not-for-profit organization committed to advancing the quality and integrity of clinical and translational scientific research in gynecologic malignancies, have announced a significant milestone in their ongoing efforts to combat endometrial cancer. The first patient has been dosed in the Phase 2 combination trial of PIKTOR, a treatment regimen that integrates FTH-001 (serabelisib) and FTH-003 (sapanisertib) with paclitaxel. This marks the most advanced study to date investigating dual PI3Kα-mTORC1/2 inhibition as a means to disrupt cancer metabolism in patients with endometrial cancer.
The PI3K/AKT/mTOR signaling pathway is among the most frequently mutated pathways in human cancers and plays a crucial role in tumor metabolism and progression. Endometrial cancer exhibits the highest frequency of PI3K pathway mutations among all solid tumors, yet no approved therapies specifically target this biological vulnerability. By combining FTH-001, a PI3Kα inhibitor, with FTH-003, an mTORC1/2 inhibitor, Faeth Therapeutics aims to implement a “multi-node” approach to targeting this key metabolic pathway, potentially providing a more effective treatment option for patients who have limited therapeutic choices.
Understanding the Significance of the PIKTOR Study
The current Phase 2 study, officially titled An Open-label, Multi-Center, Phase 2 Clinical Trial Evaluating Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel, and a Substudy Evaluating PIKTOR With Paclitaxel Plus Diet, in Patients With Advanced or Recurrent Endometrial Cancer (FTH-PIK-201, GOG-3111), builds on promising findings from prior clinical investigations. A Phase 1b study previously demonstrated an 80% overall response rate (ORR) in patients with endometrioid endometrial cancer, coupled with an impressive median progression-free survival (PFS) of 11 months.
Endometrial cancer remains a leading cause of cancer-related mortality among women, with an urgent unmet need for improved treatment options, especially for those with advanced or recurrent disease who have progressed following standard first-line carboplatin-based chemotherapy. The PIKTOR trial aims to evaluate whether the combination of serabelisib and sapanisertib with paclitaxel can enhance therapeutic outcomes in this patient population.
A Closer Look at the Targeted Pathway
The PI3K/AKT/mTOR pathway is central to many cellular functions, including growth, proliferation, survival, and metabolism. Dysregulation of this pathway is implicated in the development and progression of various cancers, particularly endometrial cancer, where genetic alterations affecting PI3K signaling are exceedingly common.
FTH-001 (serabelisib) is a potent and selective PI3Kα inhibitor designed to directly target and inhibit PI3Kα activity, thereby reducing aberrant signaling that drives tumor progression. Meanwhile, FTH-003 (sapanisertib) is an mTORC1/2 inhibitor that blocks mTOR signaling, a critical regulator of protein synthesis, cell metabolism, and survival in cancer cells. By simultaneously targeting both PI3Kα and mTORC1/2, this combination therapy seeks to cut off the tumor’s ability to adapt and survive, thereby reducing resistance mechanisms that often emerge with single-agent treatments.
Strategic Collaboration to Drive Innovation in Cancer Therapy
The collaboration between Faeth Therapeutics and The GOG Foundation is instrumental in advancing this groundbreaking therapeutic approach. With over five decades of experience in clinical research, The GOG Foundation has played a pivotal role in shaping gynecologic cancer treatment strategies. Their extensive network and expertise in conducting high-quality clinical trials will be key to ensuring the success of the PIKTOR study.
Anand Parikh, J.D., Chief Executive Officer of Faeth Therapeutics, highlighted the significance of this collaboration:
“Thanks to Faeth’s ability to uncover novel metabolism-targeting strategies, we are positioned to leverage the PIKTOR approach for endometrial cancer and other solid tumors. Over its five decades, the GOG Foundation has established itself as a leading clinical partner against gynecologic cancers, and we are confident they will help us pave the way for the next generation of cancer treatments.”
Dr. David Starks, Principal Investigator and Associate Professor at Avera Cancer Institute and University of South Dakota Sanford School of Medicine, underscored the potential impact of this innovative approach:
“This unique approach to targeting cancer metabolism has demonstrated impressive early results. We look forward to this trial to hopefully confirm these early findings and perhaps transform the way we treat patients with endometrial cancer.”
Dr. Brian Slomovitz, Director of Gynecologic Oncology at Mount Sinai Medical Center and Uterine Cancer Trial Lead for GOG Partners, further emphasized the urgency of developing better treatment options:
“Endometrial cancer is the leading cause of deaths among all gynecologic cancers. Finding better treatment options remains our highest priority. We are excited to partner with Faeth Therapeutics to further investigate this novel therapeutic approach.”
The Future of Metabolism-Targeting Cancer Therapies
The PIKTOR study represents an important step forward in the quest to improve treatment options for endometrial cancer patients. If successful, this novel combination therapy could pave the way for the development of additional metabolism-targeting strategies for various solid tumors.
Furthermore, Faeth Therapeutics’ broader focus on metabolism-based interventions suggests potential future applications beyond endometrial cancer. The company’s research efforts aim to uncover novel metabolic dependencies across different tumor types, which could lead to new and more effective treatment paradigms for multiple malignancies.
The results of this Phase 2 trial will be closely watched by the oncology community, as they hold promise for not only expanding treatment options for patients with endometrial cancer but also redefining how cancer metabolism is approached as a therapeutic target. By strategically inhibiting key metabolic pathways, Faeth Therapeutics and The GOG Foundation are at the forefront of a new era in cancer treatment—one that aims to outmaneuver the adaptability of cancer cells and ultimately improve patient outcomes.
