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ACR-368 OncoSignature Assay Receives FDA Breakthrough Device Designation for Endometrial Cancer
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Key Takeaways
- ACR-368 OncoSignature assay received FDA breakthrough designation for endometrial and ovarian cancer, highlighting its potential in personalized treatment.
- ACR-368, a CHK1/CHK2 inhibitor, demonstrated significant efficacy and safety in phase 2 studies for multiple cancer types.
The indication is for patients with endometrial cancer who may benefit from treatment with ACR-368 (Acrivon Therapeutics).
The FDA granted a breakthrough device designation for the ACR-368 OncoSignature assay (Acrivon Therapeutics, Akoya Biosciences) for the identification of patients with endometrial cancer who may benefit from treatment with ACR-368 (prexasertib; Acrivon Therapeutics, Eli Lilly & Co). In November 2023, this assay was granted a breakthrough device designation for patients with ovarian cancer. These designations, according to experts, reflect a goal to provide more effective treatment or diagnosis of life-threatening conditions.1,2
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ACR-368 is a potent, selective inhibitor of CHK1 and CHK2 that has demonstrated deep and durable single-agent activity—including complete responses—in patients across several phase 2 studies that include patients with platinum-resistant ovarian cancer, squamous cell cancer of the head and neck, and anal cancer. The agent has shown strong pharmacokinetic and pharmacological properties as well as a favorable safety profile in monotherapy studies.1,2
The OncoSignature test has been evaluated in preclinical studies, including 2 separate blinded, prospectively designed studies on pretreatment tumor biopsies that were collected from past third-party phase 2 trials that enrolled patients with ovarian cancer. The device’s purpose is to assess which patients may most benefit from treatment with ACR-368 by using a predictive precision proteomics approach.1,2
At the 2024 Human Proteome Organization World Congress, a study3 demonstrated that the OncoSignature device used mass spectrometry-based quantitative phosphoproteomics profiling to identify 3 classes of functionally orthogonal candidate biomarkers predictive of sensitivity to ACR-368. The device was used for preclinical indication finding to identify endometrial cancer as a sensitive indication and was shown to discriminate between ACR-368-sensitive and non-sensitive endometrial models.3
Positive clinical data from the open-label phase 1b/2 clinical trial (NCT05548296)4, which were reported in April for ovarian and endometrial cancers and September 2024 again for endometrial cancer, demonstrated efficacy of the device. An observed overall response rate of approximately 62.5% (95% CI, 30.4-86.5) was observed as well as OncoSignature-selected patients who were predicted sensitive to ACR-368 by showing the segregation of responders in OncoSignature-positive compared with OncoSignature-negative patients (p = .009). Currently, the median duration of treatment has not yet been reached; however, the duration on study was nearly 6 months at the time of data cutoff. These data were presented at the 2024 European Society for Medical Oncology Congress.1-4
“We are pleased that the FDA has designated our ACR-368 OncoSignature assay, developed specifically to prospectively predict tumor sensitivity to ACR-368 and used in our advancing registrational-intent clinical study, as a Breakthrough Device for patients with endometrial cancer,” said Peter Blume-Jensen, M.D., Ph.D., chief executive officer, president, and founder of Acrivon Therapeutics. “This is the second such designation for our ACR-368 OncoSignature assay… The enrollment and dosing continues for both ACR-368 in our ongoing phase 2b trials, as well as for ACR-2316… We have now completed enrollment in the first 2 dose-escalation cohorts of the ACR-2316 phase 1 trial and initiated dosing in the third cohort.”1
