FDA Grants Breakthrough Device Designation to ACR-368 OncoSignature Assay for Endometrial Cancer

The FDA granted breakthrough device designation to the multiplex immunofluorescence assay OncoSignature for the identification of patients with endometrial cancer who may benefit from treatment with ACR-368 (prexasertib).1

Findings from a phase 2 study (NCT05548296) presented during the 2024 ESMO Congress demonstrated that response-evaluable patients with endometrial carcinoma who were positively identified as suitable for ACR-368 by the OncoSignature assay (n = 8) achieved a confirmed overall response rate (ORR) of 62.5% (95% CI, 30.4%-86.5%) with the agent.2 Comparatively, patients who were not identified for treatment with ACR-368 by the assay experienced a confirmed ORR of 6.7% (95% CI, 0.84%-31.8%). Data showed a segregation of responders who were positively vs negatively identified as suitable for ACR-368 by the assay in favor of the positive patients (P = .0009).

“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,” Peter Blume-Jensen, MD, PhD, chief executive officer, president, and founder of Acrivon Therapeutics, stated in a news release.1 “This is the second such designation for our ACR-368 OncoSignature assay and represents yet another powerful validation of our generative artificial intelligence–driven AP3 platform. The enrollment and dosing continues for ACR-368 in our ongoing phase 2b trials, as well as for ACR-2316, our internally-developed phase 1 asset, which is a novel, differentiated WEE1/PKMYT1 inhibitor uniquely enabled by AP3. 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.”

ACR-358 is a potent, selective small molecule CHK1/2 inhibitor.2 In May 2023, the agent received fast track designation from the FDA for the treatment of patients with platinum-resistant ovarian cancer and endometrial cancer who are positive for predicted sensitivity to the agent via the OncoSignature test.3 In December 2023, the FDA granted breakthrough device designation to the ACR-368 OncoSignature assay for the identification of patients with ovarian who may achieve a benefit with ACR-368.4

The phase 1b/2 study examined ACR-368 as monotherapy and in combination with gemcitabine in adult patients with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma.5 Treatment was based on OncoSignature status. To be eligible for enrollment, patients needed to have measurable disease per RECIST 1.1 criteria, stabilized or recovered from all prior treatment-related toxicities, an ECOG performance status of 0 or 1, a life expectancy exceeding 3 months, and adequate organ function. Patients with endometrial cancer were required to have received no more than 4 prior lines of therapy in the recurrent setting and have experienced disease progression on or been ineligible for anti–PD(L)1 therapy for advanced or metastatic disease.

The primary end points were ORR per RECIST 1.1 criteria, safety, and determining the recommended phase 2 dose of gemcitabine in combination with ACR-368. Secondary end points included duration of response (DOR), overall survival, progression-free survival, and pharmacokinetics.

Additional findings from the phase 2 study revealed that the median DOR was not yet reached among patients positively identified as suitable for ACR-368 by the OncoSignature assay.2 All responding patients remained on therapy at the time of the data presentation at ESMO.

In terms of safety, positively identified patients (n = 12) experienced any-grade treatment-related adverse effects (TRAEs) including thrombocytopenia (50%), anemia (33%), fatigue (25%), and vomiting (25%). Grade 3 or 4 TRAEs consisted of anemia (25%), neutropenia (25%), and thrombocytopenia (17%).

Any-grade TRAEs among patients who were negatively identified by the assay (n = 23) included thrombocytopenia (52%), anemia (52%), neutropenia (30%), and fatigue (30%). Grade 3 or 4 TRAEs consisted of anemia (39%), thrombocytopenia (35%), neutropenia (30%), febrile neutropenia (13%), and hypertension (4%).

References

1. Acrivon Therapeutics announces FDA has granted breakthrough device designation for ACR-368 OncoSignature assay for endometrial cancer. News release. February 5, 2025. Accessed February 5, 2025. https://ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-announces-fda-has-granted-breakthrough-0
2. A phase II study of ACR-368 in patients with ovarian (OvCa) or endometrial carcinoma (EnCa) and prospective validation of OncoSignature patient selection (NCT05548296). Ann Oncol. 2024;35(suppl 2):S564-S56. doi:10.1016/j.annonc.2024.08.805
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 February 5, 2025. https://ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-announces-fda-grants-fast-track-designation
4. 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 February 5, 2025. https://ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-announces-fda-has-granted-breakthrough
5. A study of ACR-368 in ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma. ClinicalTrials.gov. Updated October 15, 2024. Accessed February 5, 2025. https://clinicaltrials.gov/study/NCT05548296