FDA Grants FTD to Prexasertib in Ovarian/Endometrial Cancers

The FDA has granted fast track designation to prexasertib (ACR-368) in 2 indications, including for the treatment of patients with ovarian cancer and endometrial cancer, according to a press release from Acrivon Therapeutics, Inc.

According to its manufacturers, prexasertib, a selective inhibitor of CHK1 and CHK2, has demonstrated complete responses and other durable monotherapy activity in patients with platinum-resistant ovarian cancer, squamous cell cancer of the head and neck, and anal cancer across several phase 2 studies

The first designation supports the investigation of prexasertib as a single-agent treatment option for patients with locally advanced or metastatic recurrent platinum-resistant, high-grade ovarian carcinoma who have received at least 1 prior line of systemic therapy. The second designation supports the investigation of prexasertib as a monotherapy in those with recurrent high-grade endometrial carcinoma previously treated with at least 2 prior lines of systemic therapy.

Investigators are evaluating prexasertib as part of a multi-center, open-label, single-arm phase 2 trial (NCT05548296) in patients with platinum-resistant ovarian cancer, endometrial adenocarcinoma, and urothelial cancers based on sensitivity to prexasertib as determined with the OncoSignature-predictive test.

“We are pleased that the FDA has granted the [prexasertib] development program fast track designation in recognition of its potential to improve outcomes for patients with OncoSignature-positive platinum-resistant ovarian cancer and endometrial cancer,” Peter Blume-Jensen, MD, PhD, chief executive officer, president, and founder of Acrivon, said in the press release. “There is a significant unmet need for new treatments for the tumor types we are evaluating in our ongoing phase 2 trial with [prexasertib] and for which we have received fast track designation.”

According to its manufacturers, prexasertib, a selective inhibitor of CHK1 and CHK2, has demonstrated complete responses and other durable monotherapy activity in patients with platinum-resistant ovarian cancer, squamous cell cancer of the head and neck, and anal cancer across several phase 2 studies. Investigators have also noted that prexasertib demonstrated favorable safety and pharmacokinetics profiles at the recommended phase 2 dose (RP2D) of 105 mg/m² across monotherapy studies.

In the phase 2 trial of prexasertib, patients who test positive for predicted sensitivity to the agent will receive the RP2D as a single agent. Patients with negative or unevaluable test results will receive prexasertib in combination with low-dose gemcitabine as part of an exploratory phase 1b/2 cohort.

The primary end point of the monotherapy cohort is objective response rate (ORR) per RECIST v1.1 criteria, and the primary end points of the combination cohort include the adverse effects, RP2D, and ORR. Secondary end points for both cohorts include the relative dose intensity of prexasertib, overall survival, duration of response, and progression-free survival.

Patients 18 years and older with histologically confirmed, platinum-resistant, advanced high-grade serous ovarian, primary peritoneal, or fallopian tube cancer; high-grade endometrial adenocarcinoma; or advanced urothelial carcinoma are eligible for enrollment on the trial. Additional inclusion criteria include having at least 1 measurable lesion per RECIST v1.1 criteria, a willingness to provide tissue from a newly obtained tumor biopsy, an ECOG performance status of 0 or 1, and a life expectancy of longer than 3 months. Patients also need to have adequate organ function at screening and an adequate coagulation profile to enroll.

Patients who have known symptomatic brain metastases requiring more than 10 mg of prednisolone per day, receive systematic therapy or radiotherapy within 2 weeks prior to beginning study treatment, or have a history of clinically meaningful coagulopathy are not eligible for enrollment on the trial. Patients who have cardiovascular disease or a history of major surgery within 4 weeks of screening are also unsuitable for enrollment.

Reference

Acrivon Therapeutics announces FDA grants fast track designation for development of ACR-368 in platinum-resistant ovarian cancer and endometrial cancer. News release. Acrivon Therapeutics, Inc. May 9, 2023. Accessed May 16, 2023. bit.ly/42GgHES