お知らせ • Jan 08
Acrivon Therapeutics Announces Positive ACR-368 Phase 2b Endometrial Cancer Clinical Data with EU Expansion to Accelerate Enrollment, Initial ACR-2316 Clinical Data, and ACR-6840, Its Next AP3-Enabled Development Candidate, Targeting CDK11
Acrivon Therapeutics, Inc. announced significant progress across its pipeline, including updates regarding the Phase 2 ACR-368 program, initial clinical data from the ACR-2316 Phase 1 study, and the nomination of Acrivon’s next AP3-enabled preclinical development candidate, ACR-6840, a potential first-in-class, oral CDK11 inhibitor. With respect to ACR-368, a potential first-in-class CHK1 /CHK2 inhibitor, in Arm 1 of the ACR-368 Phase 2b registrational-intent trial (monotherapy BM+ subjects), an updated interim analysis (EDC data extract as of December 4, 2025) showed an ORR of 39%, and in subjects with =2 prior lines of therapy the ORR was 44%. Based on data showing higher response rates in subjects with serous endometrial cancer across Arm 1 and Arm 2 (ACR-368 with ULDG in BM- subjects), Arm 3 will now focus exclusively on subjects with serous cancer and =2 prior lines of therapy, with updated interim analysis showing a cORR of 67% in BM+ subjects (N=12) with serous EC and an interim analysis across both BM+ and BM- subjects showing a cORR of 52% (N=23) in serous subjects versus 22% (N=37) in non-serous EC subjects, all of whom received up to two prior lines of therapy including chemotherapy and anti-PD-1. Consistent with the higher cORR observed across all subjects with serous EC, BM levels were overall higher in this tumor type, and these results are consistent with serous tumors often being G1-S-deficient, leading to DNA damage repair stress and dependency on the G2-M checkpoint controlled by CHK1/CHK2. The EU Clinical Trial Application for Arm 3 of the ongoing US multicenter, registrational-intent Phase 2b trial in serous subjects with =2 prior lines of therapy and without requirement for a tumor biopsy has been submitted, with more than 20 sites selected across Germany, Italy, France and Spain, and initial patient enrollment in the EU is expected in the first quarter of 2026 while enrollment continues at previously activated US clinical sites. Arm 3 evaluates ACR-368 combined with ULDG as a sensitizer in BM-unselected subjects with serous EC who have received up to two prior lines of therapy without requirement for a tumor biopsy, and the company expects to complete enrollment in Arm 3 in the fourth quarter of 2026, with a design of up to 90 subjects and potential validation of clinical significance in as few as 40 subjects, including the possibility of earlier interim analysis. On November 12, 2025, after incorporating feedback from a Type B meeting with the FDA earlier in 2025 and based on strong rationale and preclinical studies demonstrating synergy between ACR-368 and anti-PD-L1, the company submitted the proposed protocol design for a planned Phase 3 confirmatory study evaluating ACR-368 in combination with an anti-PD-1 agent in frontline advanced or recurrent pMMR EC subjects, and no further feedback has been received from the FDA. Regarding ACR-2316, a potential first-in-class WEE1 /PKMYT1 inhibitor, a total of 33 patients were dosed across two weekly oral dosing schedules in the ongoing Phase 1 monotherapy dose-escalation study (EDC data extract as of December 22, 2025), and initial clinical data successfully established two weekly oral dosing regimens of 160 mg QD on a 3-day on /4-day off schedule and 240 mg QD on a 2-day on /5-day off weekly schedule, with a favorable tolerability profile and transient, mechanism-based hematological adverse events predominantly neutropenia. A cohort aiming to establish a bi-weekly 2-day on /12-day off dosing regimen has been initiated based on projected enhanced single-agent activity and to provide further dosing flexibility for potential future combination studies, with clinical activity observed at dose levels of 120 mg and above, including tumor shrinkage in 9 out of 20 evaluable patients, a confirmed partial response in a subject with EC, and unconfirmed partial responses in subjects with SCLC and squamous NSCLC. Details include a subject with high-grade Mullerian EC (BRCA1/2 wild type) enrolled at 120 mg who achieved a confirmed partial response and remained on therapy for 42 weeks, a subject with SCLC enrolled at 160 mg who achieved an unconfirmed partial response with initial 50% tumor shrinkage and subsequent 69% shrinkage of the target lesion, and a subject with squamous NSCLC enrolled at 240 mg and reduced to 200 mg who achieved an unconfirmed partial response later confirmed. The trial continues to focus on selected, AP3-prioritized solid tumor types. With respect to ACR-6840, a potential first-in-class CDK11 inhibitor, the compound has been nominated as the next development candidate from the company’s AP3-driven cell cycle program, with several promising back-up series identified; CDK11 is described as a challenging but compelling target with multiple isoforms and broad cell cycle regulatory roles, and ACR-6840 was rationally designed using the AP3 platform to achieve optimal on-target pathway effects, with IND submission anticipated in the fourth quarter of 2026. Anticipated upcoming milestones include initiating EU enrollment for Arm 3 of the ACR-368 Phase 2 trial in the first quarter of 2026, providing additional updates on Arm 1 and initial clinical data from Arm 3 in mid-2026, achieving readiness for a Phase 3 confirmatory trial for ACR-368 in combination with PD-1 therapy in mid-2026, completing enrollment in the biopsy-independent Phase 2 Arm 3 trial in the fourth quarter of 2026, reporting additional ACR-2316 Phase 1 clinical data and transitioning into dose expansion in the first half of 2026, submitting an IND for ACR-6840 in the fourth quarter of 2026, and initiating additional internal programs utilizing the AP3 platform in the second half of 2026. As of December 31, 2025, the company had preliminary, unaudited cash, cash equivalents and investments of approximately $119 million, expected to fund operating expenses and capital expenditure requirements into the second quarter of 2027, noting that these amounts are preliminary and subject to completion of financial closing procedures and may differ materially from amounts reflected in the company’s consolidated financial statements for the quarter and year ended December 31, 2025.