Phase 2 Study of ACR-368 and Gemcitabine in Subjects with Endometrial Cancer
- Trial ID
- 2025-524542-10-00
- Protocol
- ACR-368-201
- Sponsor
- Acrivon Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the antitumor activity of ACR-368 in combination with ultra-low gemcitabine (ULDG) sensitization in patients with endometrial cancer. 5
Secondary objectives include:
- Assessment of safety and tolerability of the ACR-368 and ULDG combination. 4
- Evaluation of efficacy, disease control, survival, and survival landmarks via computed tomography (CT) or magnetic resonance imaging (MRI). 5
- Assessment of patient quality of life.
Participants
The study involves 281 participants diagnosed with endometrial cancer. The study population consists of female patients within specific age cohorts. Eligible subjects must have histologically documented, high-grade disease with confirmed metastatic cancer that has progressed during or after at least one prior therapeutic regimen. Participants are required to have at least one measurable lesion according to RECIST v1.1 criteria. Inclusion requires a prior history of platinum-based chemotherapy and anti-PD-(L)1 therapy, with no more than two lines of prior systemic therapy. Additionally, subjects must possess an ECOG Performance Status of 0 or 1 and an estimated life expectancy exceeding three months. The population must demonstrate adequate organ function and a stable coagulation profile. Subjects must have stabilized or recovered from prior therapy-related toxicities, with specific exceptions for alopecia, certain endocrine events, and neuropathy.
Plans and Procedures
This Phase 2 study is designed to evaluate the antitumor activity of ACR-368 in combination with gemcitabine in subjects diagnosed with endometrial cancer. The research methodology focuses on assessing the objective response rate as the primary endpoint. The clinical trial is expected to occur between April 2026 and March 2027. The study sequence begins with a screening visit to confirm eligibility, including requirements for histologically documented high-grade disease, prior platinum-based chemotherapy, and prior anti-PD-(L)1 therapy. During the trial, participants undergo evaluations to monitor adverse events, clinical laboratory parameters, and tumor response via CT scan or MRI. The study includes follow-up assessments to determine the duration of response, progression-free survival, and overall survival. Participation may be subject to early termination based on clinical judgment or protocol-defined safety and efficacy criteria.
Treatment
The investigational treatment involves prexasertib lactate monohydrate (ACR-368) provided as a vial for intravenous use. The administered dosage is 105 mg/m² via intravenous infusion.
The study also utilizes gemcitabine (GEMZAR) in the form of a solution for infusion. The dosage is 10 mg/m² administered through intravenous infusion.
Efficacy
The primary efficacy endpoint is the confirmed objective response rate (ORR) in subjects with endometrial cancer. Assessment of ORR is performed according to RECIST v1.1 using CT scan and/or MRI.
Secondary efficacy parameters include:
- Duration of response (DOR), calculated from the initial detection of an objective response until the time of assessed progressive disease, as determined by CT scan and/or MRI.
- Progression-free survival (PFS) and overall survival (OS), evaluated through Kaplan-Meier estimates based on CT scan and/or MRI.
- Clinical benefit rate (CBR), defined as the disease control rate (DCR) maintained for a minimum of 4 months via CT scan and/or MRI.
- Progression-free rate at 6 months and OS at 6, 9, and 12 months.
- Changes from baseline in scores obtained from the NRS and FACIT questionnaire.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subjects who are 18 years of age or older at time of consent.
- Subject must have an estimated life expectancy of longer than 3 months in the clinical judgement of the Investigator.
- Subject must have adequate organ function at Screening, as defined in the protocol.
- Subject must have adequate coagulation profile as defined in the protocol.
- Subject is willing and able to comply with clinical trial instructions and requirements.
- Subject must be able to give signed, written informed consent.
- Subject must have histologically documented, high-grade endometrial cancer.
- Treatment history: Subject must have received prior platinum-based chemotherapy. Subject must have received prior anti-PD-(L)1 therapy. Subject must not have received more than two lines of any type of prior systemic therapy.
- Subject must have histologically confirmed metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen. Confirmation of progression must be established using a set of imaging that will also be used to determine the presence of at least one measurable lesion.
- Subject must have at least 1 measurable lesion per RECIST v1.1 criteria (by local Investigator). Subject must have radiographic evidence of disease progression based on RECIST v1.1 criteria following the most recent line of treatment.
- For all subjects participating in Arm 3 or Arm 4, archival tumor tissue must be provided, either during or after Screening,either as a tissue block (preferred) or unstained slides .
- Subject must have stabilized or recovered (Grade 1 or baseline) from all prior therapy -related toxicities (except alopecia, endocrine events from prior immunotherapy and neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2).
- Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
- Subject received treatment with moderate or strong inhibitors of CYP1A2 within 14 days prior to the first dose of study drug. Note: Individual cases may be discussed with the Sponsor or Medical Monitor.
Exclusion Criteria
- Subject with known symptomatic brain metastases requiring > 10 mg/day of prednisolone (or its equivalent). Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to the start of ACR-368 treatment, fulfill the steroid requirement for these metastases, and are neurologically stable based on central nervous system imaging ≥ 4 weeks after treatment.
- Subject has mesenchymal tumors of the uterus.
- Subject has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis with therapeutic intent, within 4 weeks of Screening. Subjects with planned therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing are excluded.
- Subject had systemic therapy or radiation therapy within 3 weeks prior to the first dose of study drug.
- Subjects has known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection that is considered uncontrolled based on the criteria included in protocol.
- Subject has a history of clinically meaningful coagulopathy, bleeding diathesis.
- Subject has cardiovascular disease, as defined in the protocol.
- Subject has a history of major surgery within 4 weeks of Screening or a planned major elective surgery during study conduct that would significantly interfere with compliance (dose interruption of >4 weeks).
- Subject has bowel obstruction related to the current cancer within the last 4 weeks or signs or symptoms of intestinal obstruction, which include nausea, vomiting, or objective radiologic finding of bowel obstruction in the last 4 weeks before the start of the treatment.
- Subject has taken a prior cell cycle CHK1 inhibitor, including ACR-368.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 01 Apr 2026 | 24 |
 Germany | Not Yet Recruiting | 01 Apr 2026 | 12 |
 Italy | Recruiting | 01 Apr 2026 | 24 |
 Spain | Recruiting | 01 Apr 2026 | 34 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
GEMZAR 200 mg, poudre pour solution pour perfusion | Test | POUDRE POUR SOLUTION POUR PERFUSION | INTRAVENOUS INFUSION | 10 | 12 | PRD12406532 |
ACR-368 | Test | VIAL FOR INTRAVENOUS USE | INTRAVENOUS INFUSION | 105 | 12 | PRD13123002 |