Acrivon Therapeutics Inc. (NASDAQ: ACRV) unveiled new information on its development pipeline on Thursday, highlighting progress in the ACR-368 and ACR-2316 clinical programs while seeing its stock price plunge substantially.
The updates centered on an interim analysis from the Phase 2b trial of ACR-368 targeted at patients with endometrial cancer and preliminary Phase 1 findings from the dose-escalation study of ACR-2316 among lung cancer subjects.
Phase 2b ACR-368 Trial Reports Notable Response Rates In Endometrial Cancer
The company reported that Arm 1 of the Phase 2b study, which carries registrational intent, demonstrated an overall response rate (ORR) of 39% during an updated interim review. This figure increased to 44% in patients who had undergone more than two previous lines of therapy, indicating a potentially stronger response in heavily pretreated subpopulations.
Acrivon further disclosed differentiation in responses based on histological subtypes of endometrial cancer. Subjects diagnosed with serous endometrial cancer, also referred to as uterine serous carcinoma, exhibited higher response frequencies across Arms 1 and 2. This observation led the company to modify the trial’s design, focusing Arm 3 exclusively on patients with serous endometrial cancer who have received two or fewer prior treatments.
Significantly, within the biomarker-positive cohort (BM+, N=12) with serous histology, the confirmed ORR was reported at 67%, demonstrating a notable efficacy signal in this subgroup.
When expanding the interim analysis to include both biomarker-positive and biomarker-negative (BM-) serous endometrial cancer patients (N=23), the confirmed ORR stood at 52%. This rate substantially exceeds the 22% ORR observed in non-serous endometrial cancer subjects (N=37). All patients included in this comparison had up to two prior therapeutic regimens.
On the recruitment front, Acrivon indicated plans to initiate patient enrollment in Europe in the first quarter of 2026 for this Phase 2b study, alongside ongoing enrollment at activated sites in the United States.
Phase 1 ACR-2316 Trial Details Safe and Active Oral Dosing Options
For ACR-2316, a Phase 1 dose-escalation monotherapy trial involving two weekly oral regimens, the company disclosed that 33 patients had been dosed across different schedules. Initial clinical data demonstrated two tolerated oral regimens: 160 mg once daily (QD) administered on a three-days-on, four-days-off weekly cycle, and 240 mg QD dosed two days on, five days off weekly.
Both dosing schedules exhibited favorable tolerability profiles, affirming their suitability for further clinical development.
A new cohort commenced to evaluate a bi-weekly dosing regimen consisting of two days on followed by 12 days off, with the goal of enhancing single-agent activity and offering greater dosage flexibility for potential combination therapies in future studies.
Clinical activity was observed beginning at the 120 mg dose level, with tumor shrinkage documented in nine out of 20 evaluable patients. These responses were noted particularly in patients with small cell lung cancer and squamous non-small cell lung cancer subtypes.
Pipeline Expansion and Financial Status
Beyond the ongoing clinical trials, Acrivon announced the nomination of a new preclinical candidate, ACR-6840. This molecule, enabled by the company’s AP3 platform, is an oral cyclin-dependent kinase 11 (CDK11) inhibitor and could represent a first-in-class agent. An Investigational New Drug (IND) application submission is anticipated in the fourth quarter of 2026.
Financially, the company reported preliminary, unaudited cash, cash equivalents, and investments totaling approximately $119 million as of December 31, 2025. These funds are expected to sustain the company’s operating expenses and capital requirements through the second quarter of 2027.
Market Reaction
Despite the clinical advancements, Acrivon Therapeutics’ shares declined sharply on the news, falling 28.81% to $2.10 at the time of the update.
Key Points
- The Phase 2b ACR-368 trial showed a 39% overall response rate with improved results in patients with serous endometrial cancer.
- Arm 3 of the ACR-368 study will now target exclusively patients with serous histology and up to two prior therapies, following data indicating higher efficacy in this group.
- The Phase 1 trial of ACR-2316 identified two weekly dosing schedules with favorable safety and early evidence of antitumor activity in lung cancer.
- A new preclinical candidate, ACR-6840, targeting CDK11, was selected with an IND submission expected in Q4 2026.
Risks and Uncertainties
- Clinical data remain preliminary and interim; further studies are necessary to confirm efficacy and safety findings.
- Enrollment for the European segment of the ACR-368 trial is projected for early 2026, which may impact the timeline of data availability.
- Future combination studies using ACR-2316 may depend on tolerability and dose optimization yet to be fully established.
- The company's financial runway extends only through mid-2027, necessitating successful development milestones or additional funding to sustain operations.