Acrivon Therapeutics (NASDAQ:ACRV) hosted a webcast featuring a key opinion leader (KOL) panel focused on the company’s ongoing ACR-368 registrational-intent Phase 2B study in endometrial cancer, with particular attention on results in serous endometrial cancer. The panel discussion followed a late-breaking presentation at a major oncology meeting by Dana-Farber’s Panagiotis Konstantinopoulos, with data reviewed on the call by trial senior author Brian Slomovitz.
Focus on an aggressive, high-need subtype
Company leaders and KOLs repeatedly emphasized the unmet need in serous endometrial cancer, describing it as an aggressive subtype that represents a minority of endometrial cancer diagnoses but a disproportionately high share of deaths and recurrences. Peter Blume-Jensen, Acrivon’s CEO, said serous endometrial cancer is “arguably the highest unmet need” within endometrial cancer and noted it is often associated with p53 mutations and mismatch repair proficiency (pMMR). Slomovitz similarly underscored that treatment options are limited and outcomes remain poor for these patients.
Trial design and OncoSignature biomarker strategy
In the study, patients with high-grade endometrial cancer who had relapsed after prior platinum-based chemotherapy and one prior line of checkpoint inhibitor therapy were enrolled (with eligibility described as up to three lines of therapy). Patients in the biomarker-positive group received ACR-368 at 105 mg/m2 every two weeks. Biomarker-negative patients received the same ACR-368 dose combined with “ultra-low-dose” gemcitabine (ULDG) as a sensitization strategy. Slomovitz said baseline characteristics were well balanced, and he highlighted that the biomarker-positive arm had a high percentage of serous histology, suggesting a higher likelihood of biomarker positivity among serous tumors.
Reported efficacy: overall response and disease control
Slomovitz presented outcomes for the biomarker-positive intent-to-treat population, reporting:
- Overall response rate (ORR): 39%
- Disease control rate (DCR): 81%
- Clinical benefit rate (confirmed at 16 weeks): 61%
He also discussed activity by prior lines of therapy, stating the ORR was 44% among biomarker-positive patients with two prior lines or less, while the biomarker-negative group showed an ORR of 26%, which he said suggested better activity earlier in treatment.
For uterine serous cancers—described by the speakers as the area of greatest unmet need—Slomovitz reported an ORR of 52% across groups, with a DCR of 74% and a clinical benefit rate at 16 weeks of 65%. He contrasted this with non-serous patients, where he reported a 22% response rate.
In panel commentary, Robert L. Coleman compared these response rates to standard options for patients who have progressed after initial therapies, saying available treatments show response rates “at the top end around 15%.” He added that beyond response, the high rates of “lack of progression” shown in subgroup waterfall plots were encouraging for managing patients in clinic.
Safety profile and comparisons to emerging ADC therapies
On safety, Slomovitz described a “favorable” profile, citing limited and transient, mechanism-based hematologic adverse events. Domenica Lorusso said she was impressed by what she characterized as manageable toxicity, noting that 30%–40% grade 3/4 hematologic toxicity was not “scaring” for physicians and is typically easier to prevent and manage than other toxicities.
Lorusso contrasted ACR-368’s toxicity profile with challenges she said are being encountered with antibody-drug conjugates (ADCs), including interstitial lung disease, ocular toxicity, and prolonged neurotoxicity, alongside questions around optimal dose and sequencing. Panelists also discussed uncertainty around ADC target expression and biomarker cutoffs in serous endometrial cancer, and the practical difficulty of using “ADC after ADC” when many share the same payload, such as TOPO1-based payloads.
Expansion plans: serous-only cohort without biopsy requirement
Slomovitz said the company is introducing an Arm 3 cohort described as biopsy-independent and focused on serous histology patients with two or fewer prior lines of therapy, treating up to 90 patients with ACR-368 plus ULDG sensitization. The primary endpoint for this cohort is ORR. Speakers said the study is being expanded in Europe to more than 20 sites.
Lorusso said eliminating the biopsy requirement could ease recruitment because many patients do not have tumors that are easy to biopsy, and because serous disease can spread in the peritoneum, making new biopsies difficult. She also pointed to European diagnostic regulation considerations, suggesting a drug strategy not linked to a required test could simplify adoption. Mirza and Blume-Jensen said European sites were in the process of being activated, with expectations for patients to begin enrolling in early Q2, and the company reiterated a target of completing enrollment of up to 90 patients by the end of Q3.
In Q&A, the company confirmed Arm 3 allows prior ADC therapy, as it permits up to two prior lines of therapy. Blume-Jensen also said the company remains in active dialogue with the FDA and described the serous subgroup findings as a recent insight based on analyses over the past months, with prospective enrollment intended to confirm that activity holds up.
About Acrivon Therapeutics (NASDAQ:ACRV)
Acrivon Therapeutics (NASDAQ:ACRV) is a clinical-stage biotechnology company focused on the discovery and development of stapled peptide therapeutics for the treatment of RAS-driven cancers. Its proprietary platform is designed to enhance the stability, cell permeability and target specificity of peptide molecules, enabling the disruption of protein–protein interactions that are traditionally challenging to inhibit with small-molecule drugs or biologics.
The company’s lead development candidate is a hydrocarbon-stapled peptide selectively targeting the KRAS G12C mutation, currently in early clinical trials.
