FDA Grants FTD to ACR-368 for Platinum-Resistant Ovarian and Endometrial Cancer


ACR-368 generated deep and durable responses across several phase 2 studies. The agent has now been granted fast track designations for patients with platinum-resistant ovarian cancer and endometrial cancer.

The FDA granted 2 fast track designations to ACR-368 (Prexasertib) for the treatment of patients with platinum-resistant ovarian cancer and endometrial cancer, according to Acrivon Therapeutics.1

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

Findings from previous phase 2 clinical trials evaluating ACR-368 support the designations as they showed the agent to elicit deep and durable responses, and some complete responses, in patients with solid tumors, including platinum-resistant ovarian cancer.

“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,” said Peter Blume-Jensen, MD, PhD, chief executive officer, president, and founder of Acrivon, in a 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 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.”

Image credit: © Lars Neumann  - stock.adobe.com

Image credit: © Lars Neumann - [stock.adobe.com]

The open-label, phase 1b/2 study plans to assess the efficacy and safety of ACR-368 as monotherapy or combined with low dose gemcitabine in patients with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma based on Acrivon's OncoSignature® test status.2

Enrollment in the phase 1/2 trial is open to patients 18 years or older with histologically confirmed locally advanced or metastatic cancer that has progressed during or after at least 1 prior line of therapy.2 Patients must have at least 1 measurable lesion per RECIST v1.1 criteria, provide tissue from a newly obtained tumor biopsy from an accessible tumor lesion not previously irradiated, have an ECOG performance status of 0 or 1, and a life expectancy of more than 3 months.

For patients with ovarian cancer, histologically documented, platinum-resistant, metastatic, or unresectable high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer is required, and patients with primary platinum-refractory disease are not eligible for enrollment. Other requirements include having received 1 to 6 prior lines of therapy, including at least 1 line of therapy which contained platinum-based chemotherapy and a taxane. Patients must also be candidates for single-agent treatment. Additionally, patients must have had prior treatment with bevacizumab (Avastin), unless they did not receive it based on investigator judgment.

Among patients with endometrial cancer, enrollment is open to patients with histologically documented high-grade endometrial adenocarcinoma, including grade 3 International Federation of Gynecology and Obstetrics endometrioid, serous, and clear-cell carcinoma. While patients with carcinosarcoma are eligible for enrollment, investigators included a 5% cap for those with carcinosarcoma in each cohort. Additional requirements included that patients must have received no more than 3 prior lines of therapy in the recurrent setting and must have progressed on single-agent or combination therapy with a PD-1/L1 inhibitor for advanced or metastatic disease.

Patients with histologically documented metastatic and/or unresectable urothelial carcinoma are also eligible for enrollment on the trial, including patients with variant histology, as long as the tumor is predominantly urothelial. Patients must also have 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), and have no available life-prolonging therapy.

In arm 1 of the study, patients with a positive OncoSignature test will receive ACR-386 monotherapy at the recommended phase 2 dose (RP2D) of 105 mg/m2. Patients with a negative OncoSignature test are eligible to enroll in an exploratory phase 1b/2 arm to receive ACR-368 in combination with low-dose gemcitabine.

Investigators are assessing the primary end point of overall response rate (ORR) per RECIST v1.1 criteria in the monotherapy arm, as well as adverse effects with ACR-368 plus low-dose gemcitabine, the RP2D of low-dose gemcitabine, and ORR in the combination arm.

“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. 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,” added Blume-Jensen in the press release.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, Inc. May 9, 2023. Accessed May 11, 2023. https://bit.ly/3I2xNnZ
A study of ACR-368 in ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma. ClinicalTrials.gov. Updated May 3, 2023. Accessed May 10, 2023. https://clinicaltrials.gov/ct2/show/NCT05548296
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