A Phase 2 Study of ACR-368 in Endometrial Adenocarcinoma

NCT05548296 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: ACR-368-201 (GOG 3082)
• Study Type: interventional
• Target: 401
• Locations: 5 countries
• Sites: 90

Brief Summary

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.

Conditions

Endometrial Adenocarcinoma

Keywords

Endometrial Cancer; Endometrial Neoplasm; Ultralow dose gemcitabine; ACR-368

Outcome Measures

Primary Outcomes (4)

• Arm 1: Anti-tumor activity of ACR-368 in Endometrial cancer subjects that are OncoSignature Positive.

  Assess Objective Response Rate (ORR) per RECIST v1.1 by computed tomography or magnetic resonance imaging.

  Response will be assessed every 8 weeks from baseline through 2 years or death.

• Arm 2: Anti-tumor activity of ACR-368 with ULDG sensitization in Endometrial cancer subjects that are OncoSignature Negative.

  Objective Response Rate (ORR) per RECIST v1.1 by computed tomography or magnetic resonance imaging.

  Response will be assessed every 8 weeks from baseline through 2 years or death.

• Arm 3: Anti-tumor activity of ACR-368 with ULDG sensitization in Endometrial cancer subjects (Serous All-Comers).

  Objective Response Rate (ORR) per RECIST v1.1 by computed tomography or magnetic resonance imaging.

  Response will be assessed every 8 weeks from baseline through 2 years or death.

• Arm 4: Anti-tumor activity of ACR-368 with ULDG sensitization in Endometrial cancer subjects (Serous All-Comers).

  Objective Response Rate (ORR) per RECIST v1.1 by computed tomography or magnetic

  Response will be assessed every 8 weeks from baseline through 2 years or death.

Secondary Outcomes (6)

• Arm 1 and Arm 4: Adverse Events (AEs) for ACR-368

  AEs will be assessed from baseline through 2 years or death.

• Arm 2 and Arm 3: Adverse Events (AEs) for ACR-368 with ULDG sensitization

  AEs will be assessed from baseline through 2 years or death.

• All Arms: Limited pharmacokinetic (PK) testing.

  Dose of ACR-368 at day 1 and day 15 of first cycle.

• Overall Survival (OS)

  Up to 2 years

• Duration of Response (DOR)

  Up to 2 years

Study Arms (4)

OncoSignature Positive Tumors

EXPERIMENTAL

ARM 1: Participants with OncoSignature Positive Tumors will enter a Phase 2 Simon 2-Stage Study that will assess the efficacy of ACR-368 as monotherapy.

Drug: ACR-368; Diagnostic Test: OncoSignature

OncoSignature Negative Tumors

EXPERIMENTAL

Arm 2: Participants with OncoSignature Negative Tumors will receive ACR-368 with ULDG sensitization. The Phase 2 Study will assess the efficacy and safety of ACR-368 with ULDG sensitization.

Drug: ACR-368; Drug: Gemcitabine; Diagnostic Test: OncoSignature

OncoSignature Unselected (Serous All-Comers) ACR-368 with ULDG

EXPERIMENTAL

Arm 3: Participants who are OncoSignature Unselected will receive ACR-368 with ULDG sensitization. The Phase 2 Study will assess the efficacy and safety of ACR-368 with ULDG sensitization.

Drug: ACR-368; Drug: Gemcitabine

OncoSignature Unselected (Serous All-Comers) ACR-368

EXPERIMENTAL

Arm 4: Participants who are OncoSignature Unselected will receive ACR-368. The Phase 2 Study will assess the efficacy and safety of ACR-368.

Drug: ACR-368

Interventions

ACR-368 DRUG

ACR-368 is an experimental drug

Also known as: prexasertib

OncoSignature Negative Tumors; OncoSignature Positive Tumors; OncoSignature Unselected (Serous All-Comers) ACR-368; OncoSignature Unselected (Serous All-Comers) ACR-368 with ULDG

Gemcitabine DRUG

Sensitization of tumor cells is provided through administration of ULDG

OncoSignature Negative Tumors; OncoSignature Unselected (Serous All-Comers) ACR-368 with ULDG

OncoSignature DIAGNOSTIC_TEST

Prospective prediction of drug sensitivity based on a pretreatment tumor biopsy

OncoSignature Negative Tumors; OncoSignature Positive Tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be able to give signed, written informed consent.
• Participant must have histologically documented, high-grade endometrial cancer.
• Arms 1 and 2
• 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
• Serous carcinoma or mixed tumors with a majority component of serous carcinoma or carcinosarcoma where the carcinomatous component is serous carcinoma.
• Treatment History Requirements:
• Arms 1 and 2
• 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 three lines of prior systemic therapy Arms 3 and 4
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• Subject must have received prior platinum-based chemotherapy
• Subject must have received prior anti-PD-(L)1 therapy

You may not qualify if:

• 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.
• Participant has mesenchymal tumors of the uterus.
• 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.
• Participant had systemic therapy or radiation therapy within 3 weeks prior to the first dose of study drug.
• 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.
• Participant has a history of clinically meaningful coagulopathy, bleeding diathesis.
• Participant has cardiovascular disease, defined as:
• Uncontrolled hypertension defined as blood pressure \> 160/90 mmHg at Screening confirmed by repeat (medication permitted).
• 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).
• 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).
• Participant has a history of major surgery within 4 weeks of Screening.
• 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.
• Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368

Sponsors & Collaborators

• Acrivon Therapeutics: lead
• GOG Foundation: collaborator

Study Sites (90)

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

COMPLETED

Alaska Women's Cancer Center

Anchorage, Alaska, 99508, United States

COMPLETED

HonorHealth

Phoenix, Arizona, 85016, United States

RECRUITING

Arizona Oncology Associate, PC- HOPE

Tucson, Arizona, 85711, United States

ACTIVE NOT RECRUITING

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

RECRUITING

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92037, United States

RECRUITING

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

COMPLETED

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Hoag Cancer Center

Newport Beach, California, 92663, United States

RECRUITING

UC Irvine Health

Orange, California, 92868, United States

COMPLETED

Stanford Cancer Center

Palo Alto, California, 94304, United States

RECRUITING

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

University of California Los Angeles (UCLA)

Santa Monica, California, 90404, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06520, United States

COMPLETED

Florida Gynecologic Oncology/Regional Cancer Center

Fort Myers, Florida, 33905, United States

COMPLETED

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

COMPLETED

Northwestern Medicine

Chicago, Illinois, 60611, United States

RECRUITING

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

University of Chicago Medicine

Chicago, Illinois, 60637, United States

RECRUITING

Carle Cancer Center

Urbana, Illinois, 61801, United States

RECRUITING

Ascension St. Vicent Hospital, Inc.

Indianapolis, Indiana, 46260, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52252, United States

RECRUITING

LSU Health Sciences

New Orleans, Louisiana, 70112, United States

RECRUITING

Trials365, LLC

Shreveport, Louisiana, 71103, United States

RECRUITING

American Oncology Partners of Maryland PA

Bethesda, Maryland, 20817, United States

COMPLETED

National Institutes of Health, Clinical Center

Bethesda, Maryland, 20892, United States

ACTIVE NOT RECRUITING

Holy Cross Hospital

Silver Spring, Maryland, 20910, United States

COMPLETED

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

University of Massachusetts Chan Medical School

Worcester, Massachusetts, 01605, United States

COMPLETED

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

HCA Midwest

Kansas City, Missouri, 64132, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Rutgers Cancer Institute of NJ

New Brunswick, New Jersey, 08903, United States

RECRUITING

Laura & Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

RECRUITING

New York Presbyterian Hospital-Columbia University Medical Center

New York, New York, 10032, United States

COMPLETED

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Mount Sinai Health System

New York, New York, 10128, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, 14642, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

COMPLETED

FirstHealth of the Carolinas

Pinehurst, North Carolina, 28374, United States

ACTIVE NOT RECRUITING

Gabrail Cancer Center

Canton, Ohio, 44718, United States

COMPLETED

Miami Valley Hospital South

Centerville, Ohio, 45459, United States

RECRUITING

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45267, United States

RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

COMPLETED

Ohio State University

Hilliard, Ohio, 43026, United States

RECRUITING

Stephenson Cancer Center at OU Health

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Oncology Associates of Oregon

Eugene, Oregon, 97401, United States

COMPLETED

Oregon Health & Sciences University

Portland, Oregon, 97239, United States

COMPLETED

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

ACTIVE NOT RECRUITING

West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Women & Infants Hospital

Providence, Rhode Island, 02905, United States

RECRUITING

Sanford Health

Sioux Falls, South Dakota, 57104, United States

RECRUITING

Texas Oncology-Dallas Presbyterian Hospital

Dallas, Texas, 75231, United States

COMPLETED

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

COMPLETED

Texas Oncology

Fort Worth, Texas, 76104, United States

COMPLETED

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

Swedish Cancer Center

Seattle, Washington, 98104, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

COMPLETED

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

RECRUITING

Summit Cancer Center

Spokane, Washington, 99208, United States

COMPLETED

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98684, United States

COMPLETED

Froedtert and Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Centre François Baclesse

Caen, France

NOT YET RECRUITING

Centre Léon Bérard

Lyon, France

RECRUITING

Insitute de Cancérologie de l'Ouest

Saint-Herblain, France

RECRUITING

Institute Gustave Roussy

Villejuif, France

RECRUITING

KEM | Evang. Kliniken Essen-Mitte

Essen, Germany

NOT YET RECRUITING

Universitätsklinikum Münster, Klinik für Frauenheilkunde und Geburtshilfe

Münster, Germany

NOT YET RECRUITING

Universitätsklinikum Ulm, Frauenheilunde und Geburtshilfe

Ulm, Germany

NOT YET RECRUITING

CRO Aviano

Aviano, Italy

NOT YET RECRUITING

Istituto Clinico Cannizzaro Catania

Catania, Italy

NOT YET RECRUITING

Istituto Europeo di Oncologia

Milan, Italy

NOT YET RECRUITING

Fondazione Pascale Istituto Tumori

Naples, Italy

NOT YET RECRUITING

Humanitas University

Pieve Emanuele, Italy

NOT YET RECRUITING

Policlinico Gemelli

Roma, Italy

NOT YET RECRUITING

Ospedale Mauriziano Torino

Turin, Italy

NOT YET RECRUITING

Hospital Clínic de Barcelona

Barcelona, Spain

RECRUITING

Institut Català of Oncology (ICO)

Barcelona, Spain

NOT YET RECRUITING

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, Spain

NOT YET RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

NOT YET RECRUITING

Hospital Universitario La Paz

Madrid, Spain

NOT YET RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Spain

NOT YET RECRUITING

Fundacion Instituto Valenciano de Oncologia (IVO)

Valencia, Spain

NOT YET RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

prexasertib; Gemcitabine

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Panagiotis Konstantinopoulos, MD

  Dana-Farber Cancer Institute (DFCI)

  PRINCIPAL INVESTIGATOR

• Isabelle Ray-Coquard, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mansoor Raza Mirza, MD

CONTACT

617-207-8976; ACR-368-201ClinicalTrial@acrivon.com

Jeanie Tang

CONTACT

ACR-368-201ClinicalTrial@acrivon.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants with an OncoSignature Positive test will enter the Arm 1 cohort that will assess the efficacy of ACR-368 as monotherapy in endometrial cancer. Participants with an OncoSignature Negative test will enter the Arm 2 cohort to assess the efficacy and safety of ACR-368 with ULDG sensitization. Arm 2 is completed and not enrolling. Participants without OncoSignature testing will enter an OncoSignature Unselected Arm 3 cohort to assess the efficacy and safety of ACR-368 with ULDG sensitization or in the Arm 4 cohort to assess the efficacy and safety of ACR-368 monotherapy.

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: September 21, 2022
• Study Start: August 29, 2022
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); DE (3); IT (7); ES (7); US (69)