FDA Grants Fast Track Designation to Gedatolisib for HR+/HER2- mBC


Gedatolisib has earned attention from the FDA after demonstrating encouraging efficacy and safety in a phase 1b clinical trial.

The FDA has granted fast track designation to gedatolisib, for the treatment of patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC) after progression on CDK4/6 therapy, announced Celcuity Inc, in a press release.1

"There is an urgent need for better treatment options for HR+/HER2- metastatic breast cancer patients whose disease progressed after treatment with a CDK4/6 inhibitor and endocrine therapy," said Brian Sullivan, chief executive officer and co-founder of Celcuity, in a press release. "We are very encouraged by the clinical data for gedatolisib and believe that fast track designation will facilitate our efforts to advance its development for patients as quickly as possible."

Gedatolisib, a potent, reversible dual PI3K and mTOR inhibitor, has been shown preclinically to limit the potential development of drug resistance compared with similar isoform-specific PI3K inhibitors. In a phase 1b study, gedatolisib also achieved a robust response rate and a well-tolerated treatment with manageable toxicity.

In the ongoing multicenter, open label, phase 1b B2151009 study (NCT02684032), gedatolisib has been administered in combination with either palbociclib and letrozole or palbociclib and fulvestrant to women with mBC. Approximately 141 patients have been enrolled and assigned to receive gedatolisib 180 mg/week in a 4-week cycle in combination with palbociclib 125 mg daily given for 3 out of 4 weeks in a 4-week cycle, and letrozole 2.5 mg daily in 1 experimental arm or the same doses of gedatolisib and pabocilib with fulvestrant administered intramuscularly at 500 mg on Day 1, 15 and 28 and then every 28 days. The study arms also include 2 dose-escalation and 2 dose-expansion arms.2,3

In 88 evaluable patients, the overall response rate was 60% with a 75% clinical benefit rate.2

Treatment with gedatolisib appeared to be well-tolerated during the study with most treatment-related adverse events being grade 1 or 2 in severity. The most common grade 3 or 4 TRAEs observed were stomatitis and rash. Ten percent of patients in the study discontinued gedatolisib.

Based on the encourgin phase 1b results, 2 phase 2 clinical trials are planned of gedatolisib in patients with HR-positive, HER2-negative breast cancer selected with a CELsignia PI3K Pathway Test. One study aims to investigate the treatment in 25 patients and the other aims to include 15 patients.

"Initiating clinical trials to evaluate gedatolisib in CELsignia selected patients in parallel with other CELsignia studies is very synergistic," stated Sullivan. "First, we believe this will enhance the enrollment activities for each study. Secondly, these studies provide an efficient opportunity for Celcuity to evaluate gedatolisib in CELsignia PI3K test-selected patients. Finally, it allows optimization of our overall CELsignia trial strategy. We concluded that the patients eligible for PI3K therapies may significantly overlap with the patients eligible for our clinical trial evaluating the pan-HER inhibitor, dacomitinib, and the c-MET inhibitor, crizotinib. In addition, a gedatolisib based regimen offers, we believe, a significantly more favorable safety profile than the combination of dacomitinib and crizotinib. Since we have another clinical trial evaluating a pan-HER and c-MET inhibitor, we concluded the FACT-3 clinical trial was redundant, and we have decided to discontinue it."


1. Celcuity receives fda fast track designation for gedatolisib in HR+/HER2- metastatic breast cancer and provides corporate update. News release. January 20, 2022. Accessed January 20, 2022. https://bit.ly/3nI7aui

2. Celcuity reports preliminary data from phase 1b trial of gedatolisib plus Ibrance® and endocrine therapy for patients with ER+/HER2- metastatic breast cancer and provides corporate update. News release. December 10, 2021. Accessed January 20, 2022. https://bit.ly/3nI7aui

3. A study to assess the tolerability and clinical activity of gedatolisib in combination with palbociclib/letrozole or palbociclib/fulvestrant in women with metastatic breast cancer. Clinicaltrials.gov. Accessed January 20, 2022. https://bit.ly/3FLI5ow

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