FDA Grants Breakthrough Device Designation to Assay for ACR-368 in Ovarian Cancer


The FDA granted breakthrough device designation to the ACR-368 OncoSignature assay for the identification of patients with ovarian cancer who may derive benefit from the CHK1/2 inhibitor ACR-368.



The FDA granted breakthrough device designation to the ACR-368 OncoSignature assay for the identification of patients with ovarian cancer who may derive benefit from the CHK1/2 inhibitor ACR-368 (prexasertib), according to an announcement from Acrivon Therapeutics, Inc.1

“We are pleased that our ACR-368 OncoSignature assay, developed specifically to predict tumor sensitivity to ACR-368 and used in our ongoing registrational-intent clinical study to treat patients based on OncoSignature-predicted sensitivity, has been designated by the FDA as a breakthrough device,” Peter Blume-Jensen, MD, PhD, chief executive officer, president, and founder of Acrivon Therapeutics, stated in a press release. “It is exclusively through our proprietary AP3 platform that we are able to develop these proteomic-based assays that are designed to predict the patients most likely to benefit from treatment with our drug candidates.”

ACR-368 monotherapy has been found to have activity in patients with high-grade serous ovarian, anal, and head and neck cancers.2 Investigators utilized Acrivon Predictive Precision Proteomics to identify 3 functionally orthogonal biomarkers tailored to predict response to the agent.

The assay was developed for routine processed FFPE tumor biopsies based on immunofluorescent staining of the biomarkers and involves image analysis and quantitative biomarker measurements in the nuclei of the tumor cell. If all 3 biomarker scores are higher than their prespecified thresholds, a sample is determined to be positive. The test was validated in cancer cell lines and ovarian cancer PDX models.

To test the prediction of sensitivity to ACR-368, the assay was further examined in pretreatment tumor biopsies from past clinical trials of the agent. Prior trials showed a strong concordance was found between the assay-predicted prevalence of responders to the agent and the objective response rate (ORR). Endometrial and bladder cancers were also predicted to be sensitive to the agent in approximately 30% to 40% of cases.

The assay was also examined in blinded prospectively designed studies of pretreatment biopsies from phase 2 trials of the agent conducted in patients with ovarian cancer. They found that the ORR was 47% in responders vs 58% in nonresponders and increased median progression-free survival was also observed.

“We believe this designation is the first of its kind for such an assay and represents yet another powerful validation of our AP3 platform,” Blume-Jensen added in the release. “The designation importantly also highlights meaningful potential value to patients as we continue to progress ACR-368 in the clinic.”

In May 2023, the FDA granted fast track designation to single-agent ACR-368 for use in patients with platinum-resistant ovarian cancer and endometrial cancer who are positive for predicted sensitivity to the agent using the test.3

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).4

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

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

Patients with endometrial cancer were required 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 permitted. Those with carcinosarcoma are eligible but there is 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.

Those with histologically documented metastatic and/or unresectable urothelial carcinoma are allowed to enroll, including those with variant histology if the tumor is predominantly urothelial. These patients must have received a prior platinum-based regimen in the metastatic or locally advanced setting, had progression following or ineligibility for immune checkpoint inhibitors, had progression after or ineligibility for enfortumab vedotin-ejfv (Padcev), or no available life-prolonging therapy available to them.

Patients could not have symptomatic brain metastases requiring more than 10 mg per day of prednisolone. If they failed to recover from reversible effects of prior anticancer therapy, received systemic therapy or radiation within 2 weeks of the first dose of study treatment, or had a history of clinically meaningful coagulopathy, or bleeding diathesis, they were excluded. They could not have cardiovascular disease or have undergone major surgery within 4 weeks of screening. Prior treatment with a cell cycle CHK1 inhibitor, including ACR-368, is not allowed.

Study participants with a positive assay result will be administered single-agent ACR-386 at the recommended phase 2 dose of 105 mg/m2. Those with a negative test will be allowed to enroll in an exploratory phase 1b/2 arm to receive the agent paired with low-dose gemcitabine.

The primary end point for the monotherapy arm is ORR by RECIST v1.1 criteria. Primary end points for the combination arm consist of evaluating adverse effects with ACR-368 plus low-dose gemcitabine, establishing the RP2D of low-dose gemcitabine, and assessing the ORR with the combination.


  1. Acrivon Therapeutics announces FDA has granted breakthrough device designation for ACR-368 OncoSignature assay for ovarian cancer. News release. Acrivon Therapeutics, Inc. November 28, 2023. Accessed December 4, 2023. https://ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-announces-fda-has-granted-breakthrough
  2. Murshid A, Noe C, Singh K, et al. Validation of the OncoSignature assay, an ACR-368-tailored response-predictive quantitative multiplexed immunofluorescent assay for prediction of sensitivity to the CHK1/2 inhibitor ACR-368 in individual patients with cancer. Acrivon Therapeutics, Inc. Accessed December 4, 2023. https://acrivon.com/wp-content/uploads/2023/10/Acrivon-Poster-Clinical_2023_AM_LS-FINAL.pdf
  3. 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 December 4, 2023. https://ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-announces-fda-grants-fast-track-designation
  4. A study of ACR-368 in ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma. ClinicalTrials.gov. Updated May 3, 2023. Accessed December 4, 2023. https://clinicaltrials.gov/ct2/show/NCT05548296
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