Acrivon Therapeutics Advances ACR368 for Endometrial Cancer

Acrivon Therapeutics (NASDAQ:ACRV) has unveiled promising interim clinical results for its leading drug candidate, ACR368, in the treatment of endometrial cancer. During a recent conference call, Chief Financial Officer and Head of Investor Relations, Adam Levy, outlined the company’s strategic focus on its predictive precision proteomics platform, known as AP3, which aims to enhance drug efficacy through advanced biomarker identification.

Peter Blume-Jensen, Chief Executive Officer, President, and Co-founder, emphasized that the AP3 platform utilizes mass spectrometry and computational techniques to analyze the effects of compounds on cellular signaling pathways. This innovative approach is designed to identify predictive biomarkers for drug efficacy and facilitate more effective drug discovery.

Clinical Trial Insights for ACR368

In a detailed review of the ongoing phase 2 clinical trial, Mansour Mirza, Chief Medical Officer, reported that the study is currently enrolling patients at 48 U.S. sites. This open-label, multi-center trial is targeting relapsed endometrial cancer across various histopathologies, including serous, clear cell, carcinosarcoma, and high-grade endometrioid types. Eligible participants must have previously undergone platinum-based chemotherapy and an immune checkpoint inhibitor, with a maximum of three prior systemic therapy lines permitted.

At the interim analysis, a total of 36 subjects were enrolled in Arm 1 and 16 in Arm 2. In Arm 1, which focuses on biomarker-positive ACR368 monotherapy, the company recorded an overall response rate (ORR) of 39% and a disease control rate (DCR) exceeding 80%. Mirza noted that these figures would be finalized following a blinded independent central review (BICR) at the end of enrollment.

Among biomarker-positive patients who had received up to two prior lines of therapy, the ORR was notably higher at 44%. Conversely, Arm 2, which involves biomarker-negative ACR368 combined with ultra-low dose gemcitabine (ULDG), reported an ORR of 26%. The role of ULDG as a sensitizer was supported by findings from the AP3 platform and existing preclinical and clinical evidence.

The serous subtype of endometrial cancer demonstrated particularly strong responses, with a confirmed ORR of 67% in biomarker-positive serous tumors. Acrivon highlighted a crucial finding: among serous patients with up to two prior lines of therapy, the confirmed ORR reached 52%, significantly surpassing the 22% observed in the non-serous population.

Management pointed out the significant opportunity presented by serous endometrial cancer, which accounts for approximately 40% of endometrial cancer-related deaths. Blume-Jensen cited estimates of around 20,000 serous endometrial cancer fatalities annually across the U.S. and EU, with a prevalence pool estimated between 55,000 and 60,000 patients. He noted the limited treatment options available for patients in later lines of therapy.

New Trial Arm and Phase 3 Protocol Submission

In light of the encouraging activity observed in serous disease, Acrivon has initiated Arm 3 of the trial, which evaluates ACR368 combined with ULDG in biomarker-unselected serous endometrial cancer patients who have undergone up to two prior lines of therapy. This trial is being conducted at the same 48 U.S. sites and is set to expand to more than 20 European sites in France, Germany, Italy, and Spain. Mirza characterized Arm 3 as a potential “fastest path” to regulatory approval.

Blume-Jensen further detailed that Arm 3 would adopt an all-comer approach, eliminating upfront biopsy or biomarker requirements, while allowing for retrospective OncoSignature assessments. Separately, the company submitted a phase 3 confirmatory trial protocol to the FDA on November 12, 2025. This planned double-blind, placebo-controlled trial aims to enhance progression-free and overall survival rates in patients with advanced and/or recurrent mismatch repair-proficient (pMMR) endometrial cancer by incorporating ACR368 into anti-PD-1 therapy during maintenance treatment.

The rationale for the study includes evidence of preclinical synergy between ACR368 and immunotherapy observed in mouse models.

Acrivon also provided updates on its other drug candidates. The company discussed initial observations from the phase 1 trial of ACR2316, an oral dual WEE1/PKMYT1 inhibitor. Mirza reported that 33 patients have been dosed under two weekly regimens in the ongoing study. The treatment schedules include 160 mg daily (three days on, four days off) and 240 mg daily (two days on, five days off). Early findings suggest encouraging tolerability, largely limited to transient adverse events, with no grade 3 or higher non-hematological side effects reported.

In the 160 mg cohort, no instances of grade 4 toxicity were observed, while one case of grade 4 neutropenia occurred in the 240 mg cohort. Tumor shrinkage was noted in nine out of 20 evaluable patients treated at doses of 120 mg and above, highlighting ACR2316’s potential efficacy in tumor types previously unresponsive to other WEE1/PKMYT1 inhibitors, including small cell lung cancer and squamous non-small cell lung cancer.

Finally, Levy introduced a new preclinical development candidate, ACR6840, which targets CDK11, a key regulator of the cell cycle. Initial observations suggest selectivity, potency, and preclinical anti-tumor activity, including downregulation of MCL1 and induction of apoptosis in an acute myeloid leukemia (AML) cell line. Acrivon aims to submit an Investigational New Drug (IND) application for ACR6840 in the fourth quarter of this year.

In financial remarks, Levy noted that the company concluded the quarter on December 31, 2025 with approximately $119 million in cash and investments. He reiterated that the financial figures are preliminary and unaudited, while projecting a runway extending into the second quarter of 2027.

Acrivon Therapeutics continues to focus on developing innovative therapies targeting RAS-driven cancers, utilizing its proprietary platform to enhance the efficacy of peptide therapeutics in clinical settings.