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

This is a Phase 2, multicenter, open-label, single-arm study to evaluate the efficacy and safety of sapanisertib and serabelisib (PIKTOR) with paclitaxel in participants with advanced or recurrent endometrial cancer.

Start Date12 Dec 2024

Sponsor / Collaborator

Faeth Therapeutics, Inc.

NCT05300048

/ Active, not recruitingPhase 1

A Phase 1b Study of Serabelisib in Combination with an Insulin Suppressing Diet (Study ISD) and with or Without Nab-paclitaxel in Adult Subjects with Advanced Solid Tumors with PIK3CA Mutations with or Without PTEN Loss

This study will evaluate the feasibility of optimizing the safety and tolerability of serabelisib (an investigational PI3K inhibitor) when combined with an ISD and with or without nab-paclitaxel with a goal of reducing side effects and enhancing anticancer activity.

Start Date22 Apr 2022

Sponsor / Collaborator

Faeth Therapeutics, Inc.

NCT04073680

/ Unknown statusPhase 1/2

A Phase 1b/2 Study of Serabelisib in Combination With Canagliflozin in Patients With Advanced Solid Tumors With PIK3CA or KRAS Mutations

This study aims to test the hypothesis that combining serabelisib, a PI3K alpha isoform inhibitor, with an SGLT2 inhibitor, canagliflozin will improve efficacy in the treatment of patients with advanced solid tumors.

Start Date01 Sep 2020

Sponsor / Collaborator

Petra Pharma Corp.

100 Clinical Results associated with Serabelisib

100 Translational Medicine associated with Serabelisib

100 Patents (Medical) associated with Serabelisib

Literatures (Medical) associated with Serabelisib

01 Nov 2023·Gynecologic oncology

A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer

Article

Author: Faller, Douglas V ; Han, Sileny N ; Makker, Vicky ; Jewell, Andrea ; Wenham, Robert M ; Alía, Eva María Guerra ; Sedarati, Farhad ; Raspagliesi, Francesco ; Vincent, Sylvie ; Neuwirth, Rachel ; Krell, Jonathan ; Baurain, Jean-François ; Braicu, Elena Ioana ; Su, Zhenqiang ; Oza, Amit ; Oaknin, Ana ; Scambia, Giovanni ; Colombo, Nicoletta

OBJECTIVE:

This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer.

METHODS:

Patients with histologic diagnosis of endometrial cancer (1-2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m² (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m² + oral sapanisertib 4 mg on days 2-4, 9-11, 16-18, and 23-25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1-3, 8-10, 15-17, and 22-24.

RESULTS:

Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20). The sapanisertib and sapanisertib+TAK-117 arms were closed to enrollment after futility analyses. After a median follow-up of 14.4 (paclitaxel) versus 17.2 (paclitaxel+sapanisertib) months, median progression-free survival (PFS; primary endpoint) was 3.7 versus 5.6 months (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.58-1.15; p = 0.139); in patients with endometrioid histology (n = 116), median PFS was 3.3 versus 5.7 months (HR 0.66; 95% CI 0.43-1.03). Grade ≥ 3 treatment-emergent adverse event rates were 54.0% with paclitaxel versus 89.5% paclitaxel+sapanisertib.

CONCLUSIONS:

Our findings support inclusion of chemotherapy combinations with investigational agents for advanced or metastatic disease. The primary endpoint was not met and toxicity was manageable.

TRIAL REGISTRATION:

ClinicalTrials.gov number, NCT02725268.

01 Nov 2023·European journal of medicinal chemistry

Design, synthesis and bioevaluation of PI3Kα-selective inhibitors as potential colorectal cancer drugs

Article

Author: Chen, Yuan-Si ; Lei, Li ; Ban, Yu-Juan ; Zheng, Xue-Mei ; Zhang, Ji-Quan ; Tang, Lei ; Wang, Yu-Jie ; Li, Hong-Liang ; Guo, Bing ; Wang, Jian-Ta ; Dong, Yong-Xi

The dysregulation of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin signaling pathway has been implicated in various human cancers, and isoform-selective inhibitors targeting PI3Kα have received significant interest in recent years. In this study, we have designed and synthesized three series of substituted benzoxazole derivatives based on the clinical candidate TAK-117 (8a). A detailed structure-activity relationship (SAR) study has identified the optimal compound 18a bearing a quinoxaline scaffold. Compared to the control 8a, 18a exhibited 4.4-fold more potent inhibitory activity against PI3Kα (IC₅₀: 2.5 vs 11 nM) and better isoform-selective profiles over other PI3Ks. In addition, 18a showed a 1.5-fold more potent antiproliferative effect against HCT-116 cell lines (IC₅₀: 3.79 vs 5.80 μM) and a better selectivity over the normal tissue cells. The potential antitumor mechanism and in vitro metabolic stability of 18a were also investigated. Notably, pharmacokinetic assays indicated that 18a had a higher plasma exposure, a higher maximum concentration and shorter elimination time compared to 8a.

09 Dec 2022·The oncologist

Randomized Phase II Trial of Sapanisertib ± TAK-117 vs. Everolimus in Patients With Advanced Renal Cell Carcinoma After VEGF-Targeted Therapy

Article

Author: Powles, Thomas ; Duran, Ignacio ; Sedarati, Farhad ; Hainsworth, John ; Voog, Eric ; Reeves, James ; Chen, Jingjing ; Suárez, Cristina ; Castellano, Daniel ; Czaykowski, Piotr ; Porta, Camillo ; Choueiri, Toni K

Abstract:

Background:

Sapanisertib, a dual mTORC1/2 inhibitor, may offer more complete inhibition of the PI3K/AKT/mTOR pathway than mTORC1 inhibitors, such as everolimus. This phase II study evaluated the efficacy and safety of single-agent sapanisertib and sapanisertib plus the PI3Kα inhibitor TAK-117, vs. everolimus in patients with advanced clear cell renal cell carcinoma (ccRCC) that had progressed on or after VEGF-targeted therapy.

Materials and Methods:

Patients with histologically confirmed, advanced ccRCC were randomized 1:1:1 to receive single-agent everolimus 10 mg once daily, single-agent sapanisertib 30 mg once weekly, or sapanisertib 4 mg plus TAK-117 200 mg, both once daily for 3 days/week, in 28-day cycles. The primary endpoint was progression-free survival (PFS).

Results:

Ninety-five patients were treated with everolimus or sapanisertib (n = 32 each), or sapanisertib plus TAK-117 (n = 31). There were no significant differences in PFS among the 3 groups or across any subgroups. Median PFS was 3.8 months with everolimus vs. 3.6 months with sapanisertib (HR, 1.33; 95% CI, 0.75-2.36), and 3.1 months with sapanisertib plus TAK-117 (HR, 1.37; 95% CI, 0.75-2.52). No significant differences in overall survival were seen among groups. Overall response rate was 16.7%, 0%, and 7.1%, respectively. Discontinuations due to treatment-emergent adverse events were 15.6%, 28.1%, and 29.0%.

Conclusion:

Sapanisertib with or without TAK-117 was less tolerable and did not improve efficacy vs. everolimus in patients with advanced ccRCC who had relapsed after or were refractory to VEGF-targeted therapies. Dual mTORC1/2 inhibition may not be an effective therapeutic approach for these patients.

News (Medical) associated with Serabelisib

12 Mar 2025

·www.businesswire.com

Faeth Therapeutics and The GOG Foundation, Inc. (GOG-F) Launch First Phase 2 Combination Trial for Sapanisertib-Serabelisib in Patients With Endometrial Cancer

AUSTIN, Texas & PHILADELPHIA--(BUSINESS WIRE)--Faeth Therapeutics (Faeth), a clinical-stage biotechnology company focused on metabolism, and The GOG Foundation, Inc. (GOG-F), a not-for-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and translational scientific research in the field of gynecologic malignancies, today announced the first patient has been dosed in its Phase 2 combination trial of PIKTOR, which is FTH-001 (serabelisib) and FTH-003 (sapanisertib) with paclitaxel. The trial is the most advanced of its kind to investigate a novel approach of dual PI3Kɑ-mTORC1/2 inhibition targeting cancer metabolism in patients with endometrial cancer. The PI3K/AKT/mTOR pathway is the most frequently mutated pathway in cancer and is essential for tumor metabolism. Endometrial cancer has the highest frequency of PI3K pathway mutations of any solid tumor, yet there are no approved therapies addressing this need. FTH-001, a PI3Kɑ inhibitor, and FTH-003, an mTORC 1/2 inhibitor, have both demonstrated potential in multiple previous cancer clinical trials and their combination represents a unique “multi-node” approach to targeting this pathway. The current study, 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)2 will expand on the strong Phase 1b data1 showing an 80% ORR in patients with endometrioid endometrial cancer with 11 months of progression-free survival. The Phase 2 study is based on Faeth’s metabolism-focused platform for developing novel therapeutic approaches. Endometrial cancer is one of the leading causes of cancer death in women and there is a high unmet need in patients with advanced and relapsed disease who have progressed after first line carboplatin-based therapy. “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,” said Anand Parikh, J.D., Chief Executive Officer of Faeth Therapeutics. “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.” “This unique approach to target 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,” said David Starks, MD, Principal Investigator and Associate Professor, Avera Cancer Institute and University of South Dakota Sanford School of Medicine. “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,” said Brian Slomovitz, MD, Director, Gynecologic Oncology, Mount Sinai Medical Center and Uterine Cancer Trial Lead, GOG Partners. 1 Starks, David C. et al. “Phase I dose escalation study of dual PI3K/mTOR inhibition by Sapanisertib and Serabelisib in combination with paclitaxel in patients with advanced solid tumors.” Gynecologic Oncology, Volume 166, Issue 3, 403 – 409 2 https://clinicaltrials.gov/study/NCT06463028 About Faeth Therapeutics Faeth Therapeutics is a clinical-stage biotechnology company at the forefront of oncology research with a robust clinical and preclinical pipeline powered by its AI-driven MetabOS discovery platform. Faeth’s lead program, PIKTOR, has shown outstanding clinical results and is now in a Phase 2 trial for patients with endometrial cancer. For additional information, visit www.faeththerapeutics.com. About The GOG Foundation, Inc. (www.gog.org) The GOG Foundation, Inc. is a not-for-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and translational scientific research in the field of gynecologic malignancies. The GOG Foundation is committed to maintaining the highest standards in clinical trials development, execution, analysis, and distribution of results. The GOG Foundation is the only clinical trialist group in the United States that focuses its research on patients with pelvic malignancies, such as cancer of the ovary (including surface peritoneal malignancies), uterus (including endometrium, soft tissue sarcoma, and gestational trophoblastic neoplasia), cervix, and vulva. The GOG Foundation is multi-disciplinary in its approach to clinical trials, and includes gynecologic oncologists, medical oncologists, pathologists, radiation oncologists, oncology nurses, biostatisticians (including those with expertise in bioinformatics), basic scientists, quality of life experts, data managers, and administrative personnel. About GOG Partners Supported by industry, GOG Partners is structured to work directly with pharmaceutical organizations and operate clinical trials outside the National Cancer Institute (NCI) framework. The GOG Partners shares the same mission of the GOG Foundation dedicated to transforming the care in Gynecologic Oncology. By providing an alternative venue for patient accrual and site infrastructure support, GOG Partners has helped provide additional trials and opportunities for patients outside the national gynecologic clinical trials network. About Endometrial Cancer Endometrial cancer is the most common reproductive cancer affecting women within the United States, estimated to account for approximately 65,950 newly diagnosed cases in 2022. [ACS, 2022a] Although the average age at diagnosis for women with endometrial cancer is 60 years, a proportion of patients are diagnosed prior to menopause. [ACS, 2022a] Endometrial endometrioid adenocarcinoma is most commonly diagnosed when confined to the uterus, representing 67% of cases; however, the National Comprehensive Cancer Network (NCCN) reports that in 2017, 21% and 8% of cases were diagnosed as regional and distant diseases, respectively. [NCCN v1.2022c] Despite currently available treatment options, it was estimated that there would be nearly 12,550 endometrial cancer related deaths in the United States in 2022. [ACS, 2022b] Unfortunately, women with metastatic and recurrent endometrial cancer have unfavourable prognosis, with an estimated 5-year survival rate of 20%. [ACS, 2022b] aAmerican Cancer Society. Key Statistics for Endometrial Cancer. 2022, February 14. Accessed on August 4, 2022, from https://www.cancer.org/cancer/endometrial-cancer/about/key-statistics.html bAmerican Cancer Society. Survival Rates for Endometrial Cancer. 2022, February 28. Accessed August 3, 2022 from https://www.cancer.org/cancer/endometrial-cancer/detection-diagnosis-staging/survival-rates.html cNational Comprehensive Cancer Network. Uterine Neoplasms. Version 1.2022-November 4, 2021. Accessed on August 10, 2022, from https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf

Phase 2Phase 1

30 May 2024

·www.biospace.com

Faeth Therapeutics to Participate in Upcoming Jefferies Investor Conference

Faeth’s CEO to showcase how AI has unlocked metabolism as a new cancer treatment paradigm AUSTIN, Texas--(BUSINESS WIRE)-- Faeth Therapeutics, (Faeth) a clinical-stage biotechnology company, announced today that Anand Parikh, Chief Executive Officer (CEO), will participate in one-on-one investor meetings at the upcoming Jefferies Global Healthcare Conference being held June 4-6 in New York. To schedule a meeting at the conference with Faeth’s CEO, please contact bridie@faeththerapeutics.com. For more information about the conference, please contact your institutional sales representative at Jefferies. Founded by renowned oncology researchers including Drs. Lew Cantley, Siddhartha Mukherjee, and Karen Vousden alongside CEO Anand Parikh, Faeth is focused on developing therapies targeting cancer metabolism. The role of metabolism in cancer proliferation is well established, yet remains a vastly under-exploited area, with very few cancer metabolism therapies in existence today. Faeth’s differentiated approach to targeting cancer metabolism leverages a systemic understanding of cancer metabolism, functional genomics, and computational biology to develop effective, less toxic therapies. Faeth has a robust clinical and preclinical pipeline driven by the company’s MetabOS discovery platform, which leverages AI, machine learning, and curated data sets to identify targets matched to specific tumor genotypes. Faeth's lead program, FTH-001/003, or "PIKTOR," includes serabelisib, a PI3Kɑ inhibitor, and sapanisertib, an mTORC 1/2 inhibitor, which together effectively shut down the PI3K pathway, the most commonly mutated pathway in cancer. PIKTOR, together with paclitaxel, has already shown outstanding results in a Phase 1b trial including endometrial, ovarian, and breast cancers. Faeth's second clinical program features FTH-002, a specially formulated amino acid sachet, which is administered in conjunction with an amino acid-restricted regimen and radio/chemotherapy. About Faeth Therapeutics Faeth Therapeutics is a clinical-stage biotechnology company at the forefront of oncology research with a robust clinical and preclinical pipeline powered by its AI-driven MetabOS discovery platform. Faeth’s lead program, PIKTOR, has shown outstanding clinical results in a Phase 1b trial and is advancing into a Phase 2 trial in endometrial cancer in 2024. For additional information, visit .

Phase 1Phase 2Clinical Result

08 Nov 2023

·www.biospace.com

Faeth Therapeutics to Participate in the Stifel 2023 Healthcare Conference

AUSTIN, Texas--(BUSINESS WIRE)-- Faeth Therapeutics, an oncology company with clinical programs combining therapeutics with metabolic optimization to achieve greater efficacy, today announced that the company will be participating in a company presentation and 1x1 investor meetings at the Stifel 2023 Healthcare Conference, taking place from November 14-15 in New York City. Anand Parikh, J.D., Chief Executive Officer & Co-Founder, Oliver Maddocks, PhD, Head of Research & Co-Founder, and Debbie Chirnomas, MD, Chief Medical Officer, will present a company overview on Wednesday, November 15, at 3:00 pm ET. About Faeth Therapeutics Faeth Therapeutics, headquartered in Austin, TX, is a clinical-stage biotechnology company focused on bringing breakthrough research in metabolic oncology into the clinic. The company leverages its machine-learning platform to develop precision therapies, augmented by a metabolic regimen involving the patient’s diet, to revolutionize the treatment paradigm. Faeth’s lead program combines FTH-001, serabelisib, with FTH-003, sapanisertib, and an insulin suppressing regimen to slow tumor growth by shutting down the PI3K/mTOR pathway. Faeth’s scientific founders include industry leaders Drs. Lew Cantley, Sid Mukherjee, Karen Vousden. For additional information, visit .

100 Deals associated with Serabelisib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endometrial Endometrioid Adenocarcinoma	Phase 2	United States	Faeth Therapeutics, Inc.	12 Dec 2024
Colorectal Cancer	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Endometrial Carcinoma	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Head and Neck Neoplasms	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Locally Advanced Malignant Solid Neoplasm	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Lung Cancer	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
PIK3CA mutant Breast Cancer	Phase 2	-	Petra Pharma Corp.	01 Sep 2020
Metastatic Triple-Negative Breast Carcinoma	Phase 2	United States	Takeda Pharmaceutical Co., Ltd.	18 Jul 2017
Metastatic Clear Cell Renal Cell Carcinoma	Phase 2	United States	Millennium Pharmaceuticals, Inc.	30 Jun 2016
Metastatic Clear Cell Renal Cell Carcinoma	Phase 2	Canada	Millennium Pharmaceuticals, Inc.	30 Jun 2016

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03154294 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	19	paclitaxel+TAK-117+TAK-228 (Cohort 1)	oparqpzltx = esmndprnse icdtgwtuvi (qbsbixhvki, kaxuxhkeyz - lnvvifkfxs) View more	-	26 Jul 2024
				paclitaxel+TAK-117+TAK-228 (Cohort 2)	oparqpzltx = uwnjeuwcxt icdtgwtuvi (qbsbixhvki, lyulcjknko - ycneyfmuzi) View more
NCT03193853 (CTgov)	Phase 2	Metastatic Triple-Negative Breast Carcinoma	12	Nab Paclitaxel+Cisplatin+Tak-117+Tak-228	wboqhsoock = kbznicvopy ehbxpsxzie (zlylyzycpe, onqysjqeib - ddhypgzwdd) View more	-	09 May 2023
NCT03154294 (ASCO 12021 \| ASCO 22021) Manual	Phase 1	Ovarian Cancer \| Endometrial Carcinoma \| Breast Cancer PI3K Mutation \| AKT Mutation \| MTOR Mutation	19	paclitaxel+sapanisertib+serabelisib	owfqhydyyp(wfjoqbwfbe) = ppfoovkmqj qynlrwhkda (yiiekhncac ) View more	Positive	20 May 2021
NCT02724020 (CTgov)	Phase 2	Metastatic Clear Cell Renal Cell Carcinoma	96	Everolimus (Arm A: Single-agent Everolimus 10 mg QD)	bjxzqflpry(mniecofcio) = hgdnuwdnuf yqdozultgy (aeycyoclxo, xhcejwboen - twkdbxdkdu) View more	-	21 Feb 2021
				MLN0128 (Arm B: Single-agent MLN0128 30 mg QW)	bjxzqflpry(mniecofcio) = nfqzvsxyah yqdozultgy (aeycyoclxo, nzkhexxili - rvcfbwiwaf) View more
NCT02725268 (phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer, CTgov)	Phase 2	Recurrent Endometrial Cancer	241	Paclitaxel (Paclitaxel 80 mg/m^2)	rahboneexl(jiuenbcexm) = whcusgimlp sranpatixh (ggpasyoeiv, fihitcqkph - bcxvlkgspe) View more	-	09 Jun 2020
				Paclitaxel+Sapanisertib (Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg)	rahboneexl(jiuenbcexm) = zvpzvgytfp sranpatixh (ggpasyoeiv, ztmkmpxofb - bgqhmznnbf) View more
NCT01449370 (ASCO2015)	Phase 1	Advanced Malignant Solid Neoplasm	76	MLN1117 once daily (QD)	rscqjdkjaz(pgkxsaqxdl) = pfcwlzcqau qwhdydplbz (xtxmyrftjw ) View more	-	20 May 2015
				MLN1117 3 days per week (MWF)	rscqjdkjaz(pgkxsaqxdl) = nyvsyyxaah qwhdydplbz (xtxmyrftjw ) View more

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