Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

General 1. Participant must be able to give signed, written informed consent. 2. Participant must have histologically documented, high-grade endometrial cancer. 3. Treatment History Requirements: 1. Subject must have received prior platinum-based chemotherapy 2. Subject must have received prior anti-PD-(L)1 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. 7. Participant must be willing to provide an archival tumor tissue block or at least 20 unstained slides, if available. 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. 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. Calculated creatinine clearance (CrCl) ≥ 50 mL/min as calculated by the Cockcroft-Gault formula. 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 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. 10. Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
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. Participants without OncoSignature testing will enter an OncoSignature Unselected Arm 3 cohort to assess the efficacy and safety of ACR-368 with ULDG sensitization.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
OncoSignature Positive Tumors
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
    ACR-368 is an experimental drug
    Other names:
    • prexasertib
  • Diagnostic Test: OncoSignature
    Prospective prediction of drug sensitivity based on a pretreatment tumor biopsy
Experimental
OncoSignature Negative Tumors
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
    ACR-368 is an experimental drug
    Other names:
    • prexasertib
  • Drug: Gemcitabine
    Sensitization of tumor cells is provided through administration of ULDG
  • Diagnostic Test: OncoSignature
    Prospective prediction of drug sensitivity based on a pretreatment tumor biopsy
Experimental
OncoSignature Unselected (All-Comers)
Arm 3: Participants who are OncoSignature Unselected (i.e. they will not require a newly obtained tumor biopsy or OncoSignature testing) 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
    ACR-368 is an experimental drug
    Other names:
    • prexasertib
  • Drug: Gemcitabine
    Sensitization of tumor cells is provided through administration of ULDG

Recruiting Locations

HonorHealth
Phoenix 5308655, Arizona 5551752 85016
Contact:
Theresa Thomas

Arizona Oncology Associate, PC- HOPE
Tucson 5318313, Arizona 5551752 85711
Contact:
Stacey Kimbell

University of Arkansas for Medical Sciences
Little Rock 4119403, Arkansas 4099753 72205
Contact:
Maroof Zafar

City of Hope National Medical Center
Duarte 5344147, California 5332921 91010
Contact:
Lorna Rodriguez, MD

UC San Diego Moores Cancer Center
La Jolla 5363943, California 5332921 92037
Contact:
Linda Nguyen

Cedars Sinai Medical Center
Los Angeles 5368361, California 5332921 90048
Contact:
Victoria Arman

Hoag Cancer Center
Newport Beach 5376890, California 5332921 92663
Contact:
Esmerelda Martinez

Stanford Cancer Center
Palo Alto 5380748, California 5332921 94304
Contact:
Mohsin Rangwala

University of California, Davis Comprehensive Cancer Center
Sacramento 5389489, California 5332921 95817
Contact:
Apinya Vorasaph

University of California Los Angeles (UCLA)
Santa Monica 5393212, California 5332921 90404
Contact:
Rosa Vazquez

University of Colorado
Aurora 5412347, Colorado 5417618 80045
Contact:
Amelia Hardeman

Florida Gynecologic Oncology/Regional Cancer Center
Fort Myers 4155995, Florida 4155751 33905
Contact:
Samith Sandadi

Mount Sinai Comprehensive Cancer Center
Miami Beach 4164143, Florida 4155751 33140
Contact:
Evelyn Goya

Emory University
Atlanta 4180439, Georgia 4197000 30322
Contact:
Wilena Session

Northeast Georgia Medical Center
Gainesville 4196586, Georgia 4197000 30501
Contact:
Trena Davis

Northwestern Medicine
Chicago 4887398, Illinois 4896861 60611
Contact:
Peter Wojtowicz

University of Illinois Cancer Center
Chicago 4887398, Illinois 4896861 60612
Contact:
Hilda Diaz

University of Chicago Medicine
Chicago 4887398, Illinois 4896861 60637
Contact:
Amber Kindt

Carle Cancer Center
Urbana 4914570, Illinois 4896861 61801
Contact:
Kendrith Rowland

Ascension St. Vicent Hospital, Inc.
Indianapolis 4259418, Indiana 4921868 46260
Contact:
Cynthia Cruz

University of Iowa
Iowa City 4862034, Iowa 4862182 52252
Contact:
Heidi Haugland

LSU Health Sciences
New Orleans 4335045, Louisiana 4331987 70112
Contact:
Alexander Yates

Trials365, LLC
Shreveport 4341513, Louisiana 4331987 71103
Contact:
Amanda Maranto

National Institutes of Health, Clinical Center
Bethesda 4348599, Maryland 4361885 20892
Contact:
Ann McCoy, RN

Holy Cross Hospital
Silver Spring 4369596, Maryland 4361885 20910
Contact:
Sujana Lalagari

Dana Farber Cancer Institute
Boston 4930956, Massachusetts 6254926 02115
Contact:
Eleanor Estes

University of Massachusetts Chan Medical School
Worcester 4956184, Massachusetts 6254926 01605
Contact:
Dawn Pepka-Jones

Karmanos Cancer Institute
Detroit 4990729, Michigan 5001836 48201
Contact:
Robert Morris, MD, PhD

HCA Midwest
Kansas City 4393217, Missouri 4398678 64132
Contact:
Megan Werner

John Theurer Cancer Center at Hackensack University Medical Center
Hackensack 5098706, New Jersey 5101760 07601
Contact:
Lori Cappello, MSN, APN-C, CCRP

Rutgers Cancer Institute of NJ
New Brunswick 5101717, New Jersey 5101760 08903
Contact:
Karen Jackson

Laura & Isaac Perlmutter Cancer Center
New York 5128581, New York 5128638 10016
Contact:
Karen Estok

New York Presbyterian Hospital-Columbia University Medical Center
New York 5128581, New York 5128638 10032
Contact:
Reena Vattakalam

Memorial Sloan-Kettering Cancer Center
New York 5128581, New York 5128638 10065
Contact:
Chrisann Kyi, MD

Mount Sinai Health System
New York 5128581, New York 5128638 10128
Contact:
Neha Kumarley

University of Rochester Medical Center
Rochester 5134086, New York 5128638 14642
Contact:
Kelly Mateer

FirstHealth of the Carolinas
Pinehurst 4485272, North Carolina 4482348 28374
Contact:
Pamela Mason

Miami Valley Hospital South
Centerville 4508204, Ohio 5165418 45459
Contact:
Rebecca Wirth

University of Cincinnati Cancer Center
Cincinnati 4508722, Ohio 5165418 45267
Contact:
Bonny Lami

Ohio State University
Hilliard 5157588, Ohio 5165418 43026
Contact:
Kendall Lewis

Stephenson Cancer Center at OU Health
Oklahoma City 4544349, Oklahoma 4544379 73104
Contact:
Ashley Willy
phase1-referrals@ouhsc.edu

Oncology Associates of Oregon
Eugene 5725846, Oregon 5744337 97401
Contact:
Cara Ratkovich

Oregon Health & Sciences University
Portland 5746545, Oregon 5744337 97239
Contact:
Yuki Bean

West Penn Hospital
Pittsburgh 5206379, Pennsylvania 6254927 15224
Contact:
Siobhan Guyach

Women & Infants Hospital
Providence 5224151, Rhode Island 5224323 02905

Sanford Health
Sioux Falls 5231851, South Dakota 5769223 57104
Contact:
Ashley Johnson

University of Texas Southwestern Medical Center
Dallas 4684888, Texas 4736286 75390
Contact:
Annette Paulsen

Texas Oncology
Fort Worth 4691930, Texas 4736286 76104
Contact:
Lynora Sullivan

University of Texas, MD Anderson Cancer Center
Houston 4699066, Texas 4736286 77030
Contact:
Anjali Raina

Huntsman Cancer Institute, University of Utah
Salt Lake City 5780993, Utah 5549030 84112
Contact:
Celine Saenz

University of Virginia Health System
Charlottesville 4752031, Virginia 6254928 22903
Contact:
Alfredo Villalobos-Perez

Virginia Commonwealth University
Richmond 4781708, Virginia 6254928 23298
Contact:
Melanie Hamilton

Swedish Cancer Center
Seattle 5809844, Washington 5815135 98104
Contact:
Thao Amy Nguyen

Fred Hutchinson Cancer Center
Seattle 5809844, Washington 5815135 98109
Contact:
Patrick Panlasigui

Providence Sacred Heart Medical Center and Children's Hospital
Spokane 5811696, Washington 5815135 99204
Contact:
Jodie Mactagone

Northwest Cancer Specialists, P.C.
Vancouver 5814616, Washington 5815135 98684
Contact:
Margaret Bigler

Froedtert and Medical College of Wisconsin
Milwaukee 5263045, Wisconsin 5279468 53226
Contact:
Subarna Paul

More Details

NCT ID
NCT05548296
Status
Recruiting
Sponsor
Acrivon Therapeutics

Study Contact

Mansoor Raza Mirza, MD
617-207-8976
ACR-368-201ClinicalTrial@acrivon.com

Detailed Description

OncoSignature Selected Cohorts (Arms 1 and 2): Participants in Arms 1 & 2 will be allocated into two arms based on prospectively predicted sensitivity to ACR-368 using the OncoSignature® Companion Diagnostic test, as follows: Arm 1: OncoSignature Positive tumors Arm 2: OncoSignature Negative tumors OncoSignature Unselected Cohort (Arm 3): In Arm 3 participants will not require a biopsy or OncoSignature result. Participants in Arm 1 will receive ACR-368 as monotherapy. Participants in Arms 2 and 3 will receive ACR-368 with ULDG sensitization. Participants in all arms will be treated until disease progression, unacceptable toxicity or any criterion for stopping the study drug or withdrawal from the trial occurs.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.