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Evaluating ACR-368 for treating certain types of cancer

A Phase 2 Study of ACR-368 Therapy in Subjects With Endometrial Cancer

Phase 2 Interventional Acrivon Therapeutics · NCT05548296

This study is testing a new cancer drug called ACR-368, alone or with a low dose of another medication, to see if it helps people with certain hard-to-treat cancers like ovarian, endometrial, and bladder cancer.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment401 (estimated)
Ages18 Years and up
SexFemale
SponsorAcrivon Therapeutics Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy, radiation
Locations90 sites (Mobile, Alabama and 89 other locations)
Trial IDNCT05548296 on ClinicalTrials.gov

What this trial studies

This open-label Phase 1b/2 study aims to assess the efficacy and safety of ACR-368, either alone or in combination with ultralow dose gemcitabine, in patients with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma. Participants will be selected based on their OncoSignature® test results, which predict the potential effectiveness of ACR-368. Those with OncoSignature positive tumors will receive ACR-368 monotherapy, while those with negative results will receive a combination treatment. The study will continue until disease progression or unacceptable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates include individuals with histologically confirmed platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, or urothelial carcinoma who have progressed after at least one prior treatment.

Not a fit: Patients with cancers that are amenable to curative surgery or radiation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat cancers.

How similar studies have performed: Other studies have shown promise with similar targeted therapies, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria: General

1. Participant must be able to give signed, written informed consent.
2. Participant must have histologically documented, high-grade endometrial cancer.

   Arms 1 and 2
   1. All high-grade epithelial endometrial histological subtypes are eligible including: endometrioid (all Grade 3), serous, carcinosarcomas, clear-cell carcinoma, and mixed histologies.

      Note: Subjects with p53 mutant Grade 2 endometrioid cancer are eligible

      Arms 3 and 4
   2. Serous carcinoma or mixed tumors with a majority component of serous carcinoma or carcinosarcoma where the carcinomatous component is serous carcinoma.
3. Treatment History Requirements:

   Arms 1 and 2
   1. Subject must have received prior platinum-based chemotherapy
   2. Subject must have received prior anti-PD-(L)1 therapy
   3. Subject must not have received more than three lines of prior systemic therapy Arms 3 and 4

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   1. Subject must have received prior platinum-based chemotherapy
   2. Subject must have received prior anti-PD-(L)1 therapy
   3. Subject must not have received more than two lines of prior systemic therapy
4. Participant must have histologically confirmed metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.
5. Participant must have at least 1 measurable lesion per RECIST v1.1 criteria (by local Investigator) in a baseline tumor imaging that has been obtained within 28 days of the treatment start. Participant must have radiographic evidence of disease progression based on RECIST v1.1 criteria following the most recent line of treatment.
6. Arm 1 and 2 only: Participant must be willing to provide tissue from a newly obtained tumor biopsy from an accessible tumor lesion not previously irradiated after written informed consent.

   Newly obtained is defined as a specimen taken after written informed consent is obtained, during the 28-day Screening period.

   Note: Subjects at EU sites are not eligible for Arm 1 and Arm 2
7. For all subjects participating in Arm 3 and 4, archival tumor tissue must be provided either during or after screening either as a tissue block or at least 20 unstained slides.
8. Participant must have stabilized or recovered (Grade 1 or baseline) from all prior therapy related toxicities, except as follows:

   1. Alopecia is accepted.
   2. Endocrine events from prior immunotherapy stabilized at ≤ Grade 2 due to need for replacement therapy are accepted (including hypothyroidism, diabetes mellitus, or adrenal insufficiency).
   3. Neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2 are accepted.
9. Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.
10. Participant must have an estimated life expectancy of longer than 3 months in the clinical judgment of the investigator.
11. Participant must have adequate organ function at Screening, defined as:

    1. Absolute neutrophil count \> 1500 cells/µL without growth factor support within 1 week prior to obtaining the hematology values at Screening.
    2. Hemoglobin ≥ 9.0 g/dL.
    3. Platelets ≥ 150,000 cells/µL without transfusion within 1 week prior to obtaining the hematology values at Screening.
    4. Renal function is defined as Glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m2. Note: GFR may be estimated using site standard methods (e.g., CKD-EPI, MDRD, or Cockcroft-Gault) or measured using 24-hour urine collection or Chrome-EDTA clearance, as per site standard practice.
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); ≤ 5 × ULN if liver metastases are present.
    6. Total bilirubin ≤ 1.5 × ULN not associated with Gilbert's syndrome. If associated with Gilbert's syndrome ≤ 3 x ULN is acceptable.
    7. Serum albumin ≥ 3 g/dL.
12. Participant must have adequate coagulation profile as defined below if not on anticoagulation. If subject is receiving anticoagulation therapy, then subject must be on a stable dose of anticoagulation for ≥ 1 month:

    1. Prothrombin time within 1.5 x ULN.
    2. Activated partial thromboplastin time within 1.5 x ULN.

Exclusion Criteria: General

1. Participant with known symptomatic brain metastases requiring \> 10 mg/day of prednisolone (or its equivalent). Participants 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.
2. Participant has mesenchymal tumors of the uterus.
3. Participant has a history of clinically meaningful ascites, defined as 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.
4. Participant had systemic therapy or radiation therapy within 3 weeks prior to the first dose of study drug.
5. Participants has known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection that is considered uncontrolled based on the criteria included in Appendix 2.
6. Participant has a history of clinically meaningful coagulopathy, bleeding diathesis.
7. Participant has cardiovascular disease, defined as:

   1. Uncontrolled hypertension defined as blood pressure \> 160/90 mmHg at Screening confirmed by repeat (medication permitted).
   2. History of torsades de pointes, significant Screening electrocardiogram (ECG) abnormalities, including ventricular rhythm disturbances, unstable cardiac arrhythmia requiring medication, pathologic symptomatic bradycardia, left bundle branch block, second degree atrioventricular (AV) block type II, third degree AV block, Grade ≥ 2 bradycardia, uncorrected hypokalemia not amenable to correction, congenital long QT syndrome, prolonged QT interval due to medications, corrected QT based on Fridericia's formula (QTcF) \> 450 msec (for men) or \> 470 msec (for women).
   3. Symptomatic heart failure (per New York Heart Association guidelines; (Caraballo, 2019), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction \< 20%, transient ischemic attack, or cerebrovascular accident within 6 months of Day 1).
8. Participant has a history of major surgery within 4 weeks of Screening.
9. Participant has experienced 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.
10. Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368

Where this trial is running

Mobile, Alabama and 89 other locations

+40 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Endometrial AdenocarcinomaEndometrial CancerEndometrial NeoplasmUltralow dose gemcitabineACR-368
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.