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Back|NCT05548296Recruiting
Official Title

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

Phase
Phase 2
Sponsor
Acrivon Therapeutics
Enrollment
353
Timeline
Aug 2022 → Apr 2027
About This Study

This is an open label Phase 2 study to evaluate the efficacy and safety of ACR-368 as monotherapy or with ultra-low dose gemcitabine (ULDG) sensitization in participants with endometrial cancer.

Eligibility Criteria

Inclusion Criteria

  • 1Participant must be able to give signed, written informed consent.
  • 2Participant must have histologically documented, high-grade endometrial cancer.
  • 3Treatment History Requirements:
  • 4Subject must have received prior platinum-based chemotherapy
  • 5Subject must have received prior anti-PD-(L)1 therapy
  • 6Participant must have histologically confirmed metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.
  • 7Participant 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.
  • 8Arm 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.
  • 9Newly obtained is defined as a specimen taken after written informed consent is obtained, during the 28-day Screening period.
  • 10Participant must be willing to provide an archival tumor tissue block or at least 20 unstained slides, if available.
  • 11Participant must have stabilized or recovered (Grade 1 or baseline) from all prior therapy related toxicities, except as follows:
  • 12Alopecia is accepted.
  • 13Endocrine events from prior immunotherapy stabilized at ≤ Grade 2 due to need for replacement therapy are accepted (including hypothyroidism, diabetes mellitus, or adrenal insufficiency).
  • 14Neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2 are accepted.
  • 15Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.
  • 16Participant must have an estimated life expectancy of longer than 3 months.
  • 17Participant must have adequate organ function at Screening, defined as:
  • 18Absolute neutrophil count \> 1500 cells/µL without growth factor support within 1 week prior to obtaining the hematology values at Screening.
  • 19Hemoglobin ≥ 9.0 g/dL.
  • 20Platelets ≥ 150,000 cells/µL without transfusion within 1 week prior to obtaining the hematology values at Screening.
  • 21Calculated creatinine clearance (CrCl) ≥ 50 mL/min as calculated by the Cockcroft-Gault formula.
  • 22Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); ≤ 5 × ULN if liver metastases are present.
  • 23Total bilirubin ≤ 1.5 × ULN not associated with Gilbert's syndrome. If associated with Gilbert's syndrome ≤ 3 x ULN is acceptable.
  • 24Serum albumin ≥ 3 g/dL.
  • 25Participant 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:
  • 26Prothrombin time within 1.5 x ULN.
  • 27Activated partial thromboplastin time within 1.5 x ULN.

Exclusion Criteria

  • 1Participant 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.
  • 2Participant has mesenchymal tumors of the uterus.
  • 3Participant 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.
  • 4Participant had systemic therapy or radiation therapy within 3 weeks prior to the first dose of study drug.
  • 5Participants has known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection that is considered uncontrolled based on the criteria included in Appendix 2.
  • 6Participant has a history of clinically meaningful coagulopathy, bleeding diathesis.
  • 7Participant has cardiovascular disease, defined as:
  • 8Uncontrolled hypertension defined as blood pressure \> 160/90 mmHg at Screening confirmed by repeat (medication permitted).
  • 9History 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).
  • 10Symptomatic 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).
  • 11Participant has a history of major surgery within 4 weeks of Screening.
  • 12Participant has experienced bowel obstruction related to the current cancer within the last 6 months 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.
  • 13Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368

Locations

69 sites participating in this study

Emory University

Atlanta, Georgia 30322

Recruiting

Jacqueline Brown, MD

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama 36604

Completed

Alaska Women's Cancer Center

Anchorage, Alaska 99508

Completed
Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →