FDA Grants Fast Track Designation to ACR-368 in Platinum-resistant Ovarian Cancer and Endometrial Cancer


The FDA has granted fast track designations to ACR-368 monotherapy for the treatment of patients with platinum-resistant ovarian cancer and endometrial cancer who are positive for predicted sensitivity to the agent using Acrivon Therapeutics’ OncoSignature® test.



The FDA has granted fast track designations to ACR-368 (prexasertib) monotherapy for the treatment of patients with platinum-resistant ovarian cancer and endometrial cancer who are positive for predicted sensitivity to the agent using Acrivon Therapeutics’ OncoSignature® test.1

ACR-368 is a potent, selective CHK1/2 inhibitor. The agent is currently under investigation as monotherapy or in combination with low-dose gemcitabine, based on Acrivon's OncoSignature test status, in a phase 1/2 trial (NCT05548296) in patients with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma.

“We are pleased that the FDA has granted the ACR-368 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, stated in a news release. “There is a significant unmet need for new treatments for the tumor types we are evaluating in our ongoing phase 2 trial with ACR-368 and for which we have received fast track designation. The overall 5-year survival rate is approximately 30% for patients with metastatic ovarian cancer, and less than 20% for patients with metastatic endometrial cancer.”

The phase 1/2 trial is enrolling patients at least 18 years of age with histologically confirmed locally advanced or metastatic cancer that has progressed during or after at least 1 prior line of therapy.2 All patients are required to have at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of more than 3 months.

Patients with ovarian cancer are required to have histologically documented, platinum-resistant, metastatic or unresectable high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer. Notably, those with primary platinum-refractory disease are not permitted to enroll. These patients must have received 1 to 6 prior lines of therapy, including at least 1 line of therapy containing platinum-based chemotherapy and a taxane, and they must be candidates for single-agent treatment. Prior bevacizumab (Avastin) is required, unless they did not receive it based on investigator judgement.

Patients with endometrial cancer need to have histologically documented high-grade endometrial adenocarcinoma. Those with grade 3 International Federation of Gynecology and Obstetrics endometrioid, serous, and clear-cell carcinoma are allowed to enroll. Patients with carcinosarcoma are eligible; however, investigators are including a 5% cap for those with carcinosarcoma in each cohort. Patients must have received no more than 3 prior lines of therapy in the recurrent setting. Progression on single-agent or combination therapy with a PD-1/L1 inhibitor for advanced or metastatic disease is required.

Additionally, patients with histologically documented metastatic and/or unresectable urothelial carcinoma are permitted to enroll, including those with variant histology if the tumor is predominantly urothelial. Inclusion criteria for those with urothelial carcinoma include a prior platinum-based regimen in the metastatic or locally advanced setting, progression following or ineligibility for immune checkpoint inhibitors, progression after or ineligibility for enfortumab vedotin-ejfv (Padcev), or the lack of an available life-prolonging therapy.

Key exclusion criteria for all patients include symptomatic brain metastases requiring more than 10 mg per day of prednisolone; failure to recover from reversible effects of prior anticancer therapy; systemic therapy or radiation within 2 weeks or first study treatment;a history of clinically meaningful coagulopathy, bleeding diathesis; cardiovascular disease; or major surgery within 4 weeks of screening. Prior treatment with a cell cycle CHK1 inhibitor, including ACR-368, is not permitted.

Study participants with a positive OncoSignature test will receive ACR-386 monotherapy at the recommended phase 2 dose (RP2D) of 105 mg/m2. Those who have a negative OncoSignature test are allowed to enroll in an exploratory phase 1b/2 arm to receive ACR-368 in combination with low-dose gemcitabine.

The primary end point for the monotherapy arm is overall response rate (ORR) per RECIST v1.1 criteria. Primary end points for the combination arm consist of adverse effects with ACR-368 plus low-dose gemcitabine, establishing the RP2D of low-dose gemcitabine, and ORR with the combination.

“By being able to test whether a patient’s disease is likely to be sensitive to the drug’s mechanism of action, we can increase the potential for efficiently halting or reversing the course of the disease,” added Blume-Jensen in the news release. “Our approach to drug development is founded in this goal, and we have shown that the ACR-368 OncoSignature test was able to predict drug responders in blinded, prospectively designed studies on pretreatment tumor biopsies collected from past clinical trials and in patient-derived xenograft studies. We look forward to continuing this important work and to collaborating with the FDA on the advancement of ACR-368.”

Previously, ACR386 was evaluated in 28 patients with BRCA wild-type, recurrent, high-grade serous ovarian cancer as part of a first-in-class, proof-of-concept, phase 2 study (NCT02203513).3 Although all patients received at least 1 dose of the investigative agent, 4 of the patients were not response evaluable. Data indicated that 33% (95% CI, 16%-55%) of the 24 evaluable patients achieved partial responses (PRs) to the treatment. The PR rate in the intention-to-treat population was 29% (95% CI, 13%-49%).

Regarding safety, the most common grade 3 or 4 treatment-emergent toxicities observed with the agent in the total population included neutropenia (93%), decreased white blood cell count (82%), thrombocytopenia (25%), and anemia (11%). Twenty-two patients experienced neutropenia that was grade 4 in severity, although this was determined to be transient with all cases recovering without growth-factor intervention.

The agent has also been explored in heavily patients with advanced squamous cell carcinoma (SCC) as part of a phase 1b trial (NCT01115790).4 In 26 patients with SCC of the anus, ACR386 resulted in a median progression-free survival (PFS) of 2.8 months (90% CI, 1.9-4.2). In those with SCC of the head and neck (n = 57) and in those with squamous cell non–small cell lung cancer (n = 16), the median PFS with the agent was 1.6 months (90% CI, 1.4-2.8) and 3.0 months (90% CI, 1.4-3.9), respectively. The clinical benefit rates in these 3 groups were 23%, 28%, and 44%, respectively.


  1. 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. May 9, 2023. Accessed May 9, 2023.
  2. A study of ACR-368 in ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma. Updated May 3, 2023. Accessed May 9, 2023.
  3. L J-M, Nair J, Zimmer A, et al. Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study. Lancet Oncol. 2018;19(2):207-215. doi:10.1016/S1470-2045(18)30009-3
  4. Hong DS, Moore K, Patel M, et al. Evaluation of prexasertib, a Checkpoint Kinase 1 inhibitor, in a phase 1b study of patients with squamous cell carcinoma. Clin Cancer Res. 2018;24(14):3263-3272. doi:10.1158/1078-0432.CCR-17-3347

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