FDA Grants Gedatolisib Fast Track Designation for HR+/HER2- Metastatic Breast Cancer


The FDA has given a fast track designation to gedatolisib as a treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

Gedatolisib has earned a fast track designation from the FDA as a treatment for patients with hormone receptor (HR)–positive/HER2-negative metastatic breast cancer who have progressed on CDK4/6 therapy and endocrine therapy, according to a press release from Celcuity Inc.1

The company expects to receive feedback on the phase 3 clinical trial design during the first quarter of 2022. The company also has plans to initiate 2 phase 2 trials to assess the drug in patients who have been selected using the CELsignia PI3K pathway test.

“There is an urgent need for better treatment options for [patients with HR-positive/HER2-negative] metastatic breast cancer whose disease progressed after treatment with a CDK4/6 inhibitor and endocrine therapy. 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,” Brian Sullivan, chief executive officer and co-founder of Celcuity, said in the press release.

The first clinical trial will evaluate gedatolisib in combination with fulvestrant in 25 patients with metastatic disease, and the study will treat 15 patients with early-stage breast cancer with a regimen consisting of gedatolisib, palbociclib (Ibrance), and letrozole. Patients with hyperactive HER2 signaling can receive anti-HER2 therapy, while those with hyperactive PI3K signaling will receive gedatolisib in combination with other targeted therapies. The benefit of conducting these 2 studies simultaneously will be to enhance screening activities for patients who may be eligible for treatment.

In a presentation from the 2021 San Antonio Breast Cancer Symposium, the results of a phase 1b trial (NCT02684032) showed a robust response rate and tolerable adverse effect profile for the combination of gedatolisib plus palbociclib and endocrine therapy in a population of patients with estrogen receptor–positive/HER2-negative advanced breast cancer.2

A total of 35 patients were enrolled into the dose escalation cohort in which they were treated with either a regimen of palbociclib, letrozole, and gedatolisib, or palbociclib, fulvestrant, and gedatolisib. The trial also included an expansion cohort with 103 patients and 4 treatment arms. In arm A, patients had first-line therapy that consisted of palbociclib, letrozole, and gedatolisib. In arm B, patients in the second line who were CDK inhibitor–naïve received palbociclib, fulvestrant, and gedatolisib. Patients in arm C, who were in their second- or third-line of therapy and had previously undergone treatment with a CDK inhibitor, received a regimen of palbociclib, fulvestrant, and gedatolisib weekly. In arm D, patients received palbociclib, fulvestrant, and gedatolisib with a 3 weeks on, 1 week off schedule.

Patients received 125 mg of palbociclib a day with 3 weeks on and 1 week off; letrozole at 2.5 mg per day; fulvestrant at a dose of 500 mg via intramuscular injection on cycle 1 on days 1 and 15 every 28 days plus or minus 3 days moving forward; and gedatolisib intravenously at 180 mg weekly for arms A, B, and C, and 3 weeks on, 1 week off for arm D.

The most common reasons for discontinuing treatment across all arms were reasons other than adverse effects (AEs) and disease progression. At the time of cutoff, 11 patients in arm A, 3 in arm B, none in arm C, and 3 in arm D were still receiving treatment.

Patients in arm A had an overall response rate (ORR) of 85% and a median progression-free survival (PFS) of 31.1 months. Arm B, the population of which had received prior endocrine therapy without a CDK4/6 inhibitor, had an ORR of 77% and a median PFS of 11.9 months. In arm C, the population of whom 66% had received 2 or more lines of prior therapy, achieved an ORR was 32% with a median PFS of 5.1 months. Finally, arm D achieved an ORR of 63% and a median PFS of 12.9 months; thirty-three percent of patients in the arm had received 2 or more previous lines of therapy.

The most common grade 3 treatment-related and treatment emergent AEs were neutropenia or neutrophil count decrease (53%), stomatitis (27%), maculo-papular rash (14%), and leukopenia (13%). Grade 4 toxicities included neutropenia or neutrophil count decrease (14%), leukopenia (3%), hyperglycemia (2%), and lymphocyte count decrease (1%).


1. Celcuity receives FDA fast track designation for gedatolisib in HR+/HER2- metastatic breast cancer and provides corporate update. News Release. Celcuity. January 18, 2022. Accessed January 25, 2022. https://yhoo.it/3rS17om

2. Layman RM, Wesolowski R, Han H, et al. Phase 1b expansion study of gedatolisib in combination with palbociclib and endocrine therapy in women with ER+ advanced breast cancer. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract 1017. https://bit.ly/3ry0qjZ

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