Endometrial AdenocarcinomaPhase 2NCT05548296
A Phase 2 Study of ACR-368 in Endometrial Adenocarcinoma
A Phase 2 study testing ACR-368, Gemcitabine and OncoSignature in people with Endometrial Adenocarcinoma, run by Acrivon Therapeutics at 90 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Adenocarcinoma
- What is being tested?
- ACR-368, Gemcitabine and OncoSignature
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 90 sitesin 5 countries
- Study dates
- 29 Aug 2022to 30 Nov 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Subject must not have received more than two lines of prior systemic therapy
- Participant must have histologically confirmed metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.
- 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.
- 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
- 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.
- Participant must have stabilized or recovered (Grade 1 or baseline) from all prior therapy related toxicities, except as follows:
- Alopecia is accepted.
- Endocrine events from prior immunotherapy stabilized at ≤ Grade 2 due to need for replacement therapy are accepted (including hypothyroidism, diabetes mellitus, or adrenal insufficiency).
- Neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2 are accepted.
- Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.
- Participant must have an estimated life expectancy of longer than 3 months in the clinical judgment of the investigator.
- Participant must have adequate organ function at Screening, defined as:
- Absolute neutrophil count > 1500 cells/µL without growth factor support within 2 weeks prior to obtaining the hematology values at Screening.
- Hemoglobin ≥ 9.0 g/dL.
- Platelets ≥ 150,000 cells/µL without transfusion within 1 week prior to obtaining the hematology values at Screening.
- 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.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); ≤ 5 × ULN if liver metastases are present.
- Total bilirubin ≤ 1.5 × ULN not associated with Gilbert's syndrome. If associated with Gilbert's syndrome ≤ 3 x ULN is acceptable.
- Serum albumin ≥ 3 g/dL.
- 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:
- Prothrombin time within 1.5 x ULN.
- Activated partial thromboplastin time within 1.5 x ULN.
Who cannot join
- 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.
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- 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
Trial locations and contacts
90 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
Jeanie Tang contact
90 sites in 5 countries
United States69 sites, 42 recruiting
- Completed
Alaska Women's Cancer Center
Anchorage, Alaska, 99508
- Recruiting
Emory University
Atlanta, Georgia, 30322
Wilena Session
Kristen Starbuck, MD
- Recruiting
University of Colorado
Aurora, Colorado, 80045
Amelia Hardeman
Lindsay Brubaker, MD
- Completed
American Oncology Partners of Maryland PA
Bethesda, Maryland, 20817
- Active, not recruiting
National Institutes of Health, Clinical Center
Bethesda, Maryland, 20892
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Eleanor Estes
Panagiotis Konstantinopoulos, MD, PhD
- Completed
Gabrail Cancer Center
Canton, Ohio, 44718
- Recruiting
Miami Valley Hospital South
Centerville, Ohio, 45459
Rebecca Wirth
Michael Guy, MD
- Completed
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
- Recruiting
University of Virginia Health System
Charlottesville, Virginia, 22903
Alfredo Villalobos-Perez
Linda Duska, MD
- Recruiting
Northwestern Medicine
Chicago, Illinois, 60611
Peter Wojtowicz
Daniela Matei, MD
- Recruiting
University of Illinois Cancer Center
Chicago, Illinois, 60612
Hilda Diaz
Rajul Kothari, MD
- Recruiting
University of Chicago Medicine
Chicago, Illinois, 60637
Amber Kindt
John Moroney, MD
- Recruiting
University of Cincinnati Cancer Center
Cincinnati, Ohio, 45267
Bonny Lami
Caroline Billingsley, MD
- Completed
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
- Completed
Texas Oncology-Dallas Presbyterian Hospital
Dallas, Texas, 75231
- Completed
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201
Robert Morris, MD, PhD
Ira Winer, MD, PhD
- Recruiting
City of Hope National Medical Center
Duarte, California, 91010
Lorna Rodriguez, MD
Mihae Song, MD
- Completed
Oncology Associates of Oregon
Eugene, Oregon, 97401
- Completed
Florida Gynecologic Oncology/Regional Cancer Center
Fort Myers, Florida, 33905
- Completed
Texas Oncology
Fort Worth, Texas, 76104
- Completed
Northeast Georgia Medical Center
Gainesville, Georgia, 30501
- Recruiting
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Lori Cappello, MSN, APN-C, CCRP
Donna McNamara, MD
- Recruiting
Ohio State University
Hilliard, Ohio, 43026
Kendall Lewis
David O'Malley, MD
- Recruiting
University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
Anjali Raina
Funda Meric-Bernstam, MD
- Recruiting
Ascension St. Vicent Hospital, Inc.
Indianapolis, Indiana, 46260
Cynthia Cruz
Michael Callahan, MD
- Recruiting
University of Iowa
Iowa City, Iowa, 52252
Heidi Haugland
David Bender, MD
- Recruiting
HCA Midwest
Kansas City, Missouri, 64132
Megan Werner
Alaa Elbendary, DO
- Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, 92037
Linda Nguyen
Ramez Eskander, MD
- Recruiting
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Maroof Zafar
Heather Williams, MD
- Completed
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
- Recruiting
Cedars Sinai Medical Center
Los Angeles, California, 90048
Victoria Arman
Garrett Crook
- Recruiting
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140
Evelyn Goya
Brian Slomovitz, MD
- Recruiting
Froedtert and Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Subarna Paul
William Bradley, MD
- Completed
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, 36604
- Recruiting
Rutgers Cancer Institute of NJ
New Brunswick, New Jersey, 08903
Karen Jackson
Aliza Leiser, MD
- Completed
Yale Cancer Center
New Haven, Connecticut, 06520
- Recruiting
LSU Health Sciences
New Orleans, Louisiana, 70112
Alexander Yates
Amelia Jernigan, MD
- Recruiting
Laura & Isaac Perlmutter Cancer Center
New York, New York, 10016
Karen Estok
Bhavana Pothuri, MD
- Completed
New York Presbyterian Hospital-Columbia University Medical Center
New York, New York, 10032
- Recruiting
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Mauline Onsombi
Chrisann Kyi, MD
- Recruiting
Mount Sinai Health System
New York, New York, 10128
Neha Kumarley
Stephanie Blank, MD
- Recruiting
Hoag Cancer Center
Newport Beach, California, 92663
Esmerelda Martinez
Alberto Mendivil, MD
- Recruiting
Stephenson Cancer Center at OU Health
Oklahoma City, Oklahoma, 73104
Ashley Willy, phase1-referrals@ouhsc.edu
Debra Richardson, MD
- Completed
UC Irvine Health
Orange, California, 92868
- Recruiting
Stanford Cancer Center
Palo Alto, California, 94304
Mohsin Rangwala
Kirstin Bixel, MD
- Active, not recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
- Recruiting
HonorHealth
Phoenix, Arizona, 85016
Theresa Thomas
Lyndsay Willmott, MD
- Active, not recruiting
FirstHealth of the Carolinas
Pinehurst, North Carolina, 28374
- Recruiting
West Penn Hospital
Pittsburgh, Pennsylvania, 15224
Siobhan Guyach
Sarah Crafton, MD
- Completed
Oregon Health & Sciences University
Portland, Oregon, 97239
- Recruiting
Women & Infants Hospital
Providence, Rhode Island, 02905
oncologyresearch@wihri.org
Cara Mathews, MD
- Active, not recruiting
Virginia Commonwealth University
Richmond, Virginia, 23298
- Recruiting
University of Rochester Medical Center
Rochester, New York, 14642
Kelly Mateer
Rachael Turner, MD
- Recruiting
University of California, Davis Comprehensive Cancer Center
Sacramento, California, 95817
Apinya Vorasaph
Hui Chen, MD
- Recruiting
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
Celine Saenz
Theresa Werner, MD
- Recruiting
University of California Los Angeles (UCLA)
Santa Monica, California, 90404
Rosa Vazquez
Alexandra Drakaki, MD
- Recruiting
Swedish Cancer Center
Seattle, Washington, 98104
Thao Amy Nguyen
Fernanda Musa, MD
- Completed
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
- Recruiting
Trials365, LLC
Shreveport, Louisiana, 71103
Amanda Maranto
Destin Black, MD
- Completed
Holy Cross Hospital
Silver Spring, Maryland, 20910
- Recruiting
Sanford Health
Sioux Falls, South Dakota, 57104
Ashley Johnson
Maria Bell, MD
- Recruiting
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Jodie Mactagone
Melanie Bergman, MD
- Completed
Summit Cancer Center
Spokane, Washington, 99208
- Active, not recruiting
Arizona Oncology Associate, PC- HOPE
Tucson, Arizona, 85711
- Recruiting
Carle Cancer Center
Urbana, Illinois, 61801
Kendrith Rowland
Pratima Chalasani, MD
- Completed
Northwest Cancer Specialists, P.C.
Vancouver, Washington, 98684
- Completed
University of Massachusetts Chan Medical School
Worcester, Massachusetts, 01605
Italy7 sites, 7 recruiting
- Recruiting
CRO Aviano
Aviano
Michele Bartoletti, MD
- Recruiting
Istituto Clinico Cannizzaro Catania
Catania
Giuseppa Scandurra, MD
- Recruiting
Istituto Europeo di Oncologia
Milan
Nicoletta Colombo, MD
- Recruiting
Fondazione Pascale Istituto Tumori
Naples
Carmela Pisano, MD
- Recruiting
Humanitas University
Pieve Emanuele
Domenica Lorusso, MD
- Recruiting
Policlinico Gemelli
Roma
Anna Fagotti, MD
- Recruiting
Ospedale Mauriziano Torino
Turin
Giorgio Valabrega, MD
Spain7 sites, 7 recruiting
- Recruiting
Hospital Clínic de Barcelona
Barcelona
Lydia Gaba Garcia, MD
- Not yet recruiting
Hospital Universitario Puerta de Hierro
Barcelona
Ana Oaknin Benzaquen, MD
- Recruiting
Vall d'Hebron Institute of Oncology (VHIO)
Barcelona
Lorena Farinas, MD
- Recruiting
Hospital Universitario 12 de Octubre
Madrid
Luis Manuel Manso Sanchez, MD
- Recruiting
Hospital Universitario La Paz
Madrid
Andrés Redondo Sanchez, MD
- Recruiting
Hospital Universitario Ramón y Cajal
Madrid
Eva María Guerra Alia, MD
- Recruiting
Fundacion Instituto Valenciano de Oncologia (IVO)
Valencia
Ignacio Romero Noguera, MD
France4 sites, 4 recruiting
- Recruiting
Centre François Baclesse
Caen
Florence Joly-Lobbedez, MD
- Recruiting
Centre Léon Bérard
Lyon
Isabelle Ray-Coquard, MD
- Recruiting
Insitute de Cancérologie de l'Ouest
Saint-Herblain
Jean-Sebastien Frenel, MD
- Recruiting
Institute Gustave Roussy
Villejuif
Alexandra Leary, MD
Germany3 sites, 3 recruiting
- Not yet recruiting
KEM | Evang. Kliniken Essen-Mitte
Essen
Philipp Harter, MD
- Not yet recruiting
Universitätsklinikum Münster, Klinik für Frauenheilkunde und Geburtshilfe
Münster
Lars Hanker, MD
- Not yet recruiting
Universitätsklinikum Ulm, Frauenheilunde und Geburtshilfe
Ulm
Sabine Heublein, MD
About this study
Official title: A Phase 2 Study of ACR-368 Therapy in Subjects With Endometrial Cancer
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.
Read the 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 (completed)
OncoSignature Unselected Cohort (Arm 3 \& Arm 4):
In Arm 3 and Arm 4, participants will not require a biopsy or OncoSignature result.
Participants in Arm 1 and Arm 4 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.
Arms 1 and 2 do not apply to sites in the European Union (EU), which will enroll subjects in Arm 3 and Arm 4.
- Conditions
- Endometrial Adenocarcinoma
- Being tested
- ACR-368, Gemcitabine, OncoSignature
- Keywords
- Endometrial Cancer, Endometrial Neoplasm, Ultralow dose gemcitabine, ACR-368
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACR-368Drug
Also called prexasertib
ACR-368 is an experimental drug
GemcitabineDrug
Sensitization of tumor cells is provided through administration of ULDG
OncoSignatureDiagnostic test
Prospective prediction of drug sensitivity based on a pretreatment tumor biopsy
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: ACR-368 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Safety will be assessed by the incidence of AEs characterized overall and by type, incidence, severity graded according to NCI CTCAE v5.0, seriousness, and relationship to study treatment.
Measured: 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
Safety will be assessed by the incidence of AEs characterized overall and by type, incidence, severity graded according to NCI CTCAE v5.0, seriousness, and relationship to study treatment.
Measured: AEs will be assessed from baseline through 2 years or death.
All Arms: Limited pharmacokinetic (PK) testing.
Cmax and Tmax will be assessed in the first cycle. Blood samples will be collected at baseline, end of infusion, hour 2 and hour 4.
Measured: Dose of ACR-368 at day 1 and day 15 of first cycle.
Overall Survival (OS)
The time from date of enrollment until date of death.
Measured: Up to 2 years
Duration of Response (DOR)
The time from initial response until investigator assessed progressive disease for all subjects who achieve a confirmed objective response.
Measured: Up to 2 years
Progression-free Survival (PFS)
The time from date of enrollment until disease progression or death whichever occurs first.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2022
- Study start29 Aug 2022
- Primary completion30 May 2027 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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. 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.
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Acrivon Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GOG Foundation
- Responsible party
- Sponsor
- Investigators
- Panagiotis Konstantinopoulos, MD, Principal investigator, Dana-Farber Cancer Institute (DFCI)Isabelle Ray-Coquard, MD, Principal investigator, Centre Leon Berard
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05548296
- Sponsor's protocol ID
- ACR-368-201 (GOG 3082)
- Status last verified
- Jun 2026
- First submitted
- 29 Aug 2022
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of ACR-368 Therapy in Subjects With Endometrial Cancer
- ClinicalTrials.gov ID
- NCT05548296
- Acronym / sponsor ID
- ACR-368-201 (GOG 3082)
- Conditions
- Endometrial Adenocarcinoma
- Keywords
- Endometrial Cancer, Endometrial Neoplasm, Ultralow dose gemcitabine, ACR-368
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Acrivon TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- GOG Foundation
- Study start
- 29 Aug 2022 (actual)
- Primary completion
- 30 May 2027 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 21 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 (completed)
OncoSignature Unselected Cohort (Arm 3 \& Arm 4):
In Arm 3 and Arm 4, participants will not require a biopsy or OncoSignature result.
Participants in Arm 1 and Arm 4 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.
Arms 1 and 2 do not apply to sites in the European Union (EU), which will enroll subjects in Arm 3 and Arm 4.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- 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. 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.
| Arm | Type | Receives |
|---|---|---|
| OncoSignature Positive Tumors | Experimental | Drug: ACR-368, Diagnostic Test: OncoSignatureARM 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. |
| OncoSignature Negative Tumors | Experimental | Drug: ACR-368, Drug: Gemcitabine, Diagnostic Test: OncoSignatureArm 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. |
| OncoSignature Unselected (Serous All-Comers) ACR-368 with ULDG | Experimental | Drug: ACR-368, Drug: GemcitabineArm 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. |
| OncoSignature Unselected (Serous All-Comers) ACR-368 | Experimental | Drug: ACR-368Arm 4: Participants who are OncoSignature Unselected will receive ACR-368. The Phase 2 Study will assess the efficacy and safety of ACR-368. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (39 listed)
- Participant must be able to give signed, written informed consent.
- Participant must have histologically documented, high-grade endometrial cancer.
- Arms 1 and 2
- Note: Subjects with p53 mutant Grade 2 endometrioid cancer are eligible
- Arms 3 and 4
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ACR-368Also: prexasertibACR-368 is an experimental drug | Drug | OncoSignature Negative Tumors, OncoSignature Positive Tumors, OncoSignature Unselected (Serous All-Comers) ACR-368, OncoSignature Unselected (Serous All-Comers) ACR-368 with ULDG |
| GemcitabineSensitization of tumor cells is provided through administration of ULDG | Drug | OncoSignature Negative Tumors, OncoSignature Unselected (Serous All-Comers) ACR-368 with ULDG |
| OncoSignatureProspective prediction of drug sensitivity based on a pretreatment tumor biopsy | Diagnostic test | OncoSignature Negative Tumors, OncoSignature Positive Tumors |
Primary outcome
Arm 1: Anti-tumor activity of ACR-368 in Endometrial cancer subjects that are OncoSignature Positive.
Time frame: Response will be assessed every 8 weeks from baseline through 2 years or death.
Assess Objective Response Rate (ORR) per RECIST v1.1 by computed tomography or magnetic resonance imaging.
Arm 2: Anti-tumor activity of ACR-368 with ULDG sensitization in Endometrial cancer subjects that are OncoSignature Negative.
Time frame: Response will be assessed every 8 weeks from baseline through 2 years or death.
Objective Response Rate (ORR) per RECIST v1.1 by computed tomography or magnetic resonance imaging.
Arm 3: Anti-tumor activity of ACR-368 with ULDG sensitization in Endometrial cancer subjects (Serous All-Comers).
Time frame: Response will be assessed every 8 weeks from baseline through 2 years or death.
Objective Response Rate (ORR) per RECIST v1.1 by computed tomography or magnetic resonance imaging.
Arm 4: Anti-tumor activity of ACR-368 with ULDG sensitization in Endometrial cancer subjects (Serous All-Comers).
Time frame: Response will be assessed every 8 weeks from baseline through 2 years or death.
Objective Response Rate (ORR) per RECIST v1.1 by computed tomography or magnetic
6 secondary outcomes
Arm 1 and Arm 4: Adverse Events (AEs) for ACR-368
Time frame: 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
Time frame: AEs will be assessed from baseline through 2 years or death.
All Arms: Limited pharmacokinetic (PK) testing.
Time frame: Dose of ACR-368 at day 1 and day 15 of first cycle.
Overall Survival (OS)
Time frame: Up to 2 years
Duration of Response (DOR)
Time frame: Up to 2 years
Progression-free Survival (PFS)
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jeanie Tang contact
Panagiotis Konstantinopoulos, MD principal investigator
Dana-Farber Cancer Institute (DFCI)
Isabelle Ray-Coquard, MD principal investigator
Centre Leon Berard
90 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ACR-368, Gemcitabine and OncoSignature in people with Endometrial Adenocarcinoma, run by Acrivon Therapeutics at 90 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 39 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 90 sites in United States, Italy, Spain, France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mansoor Raza Mirza, MD (617-207-8976, ACR-368-201ClinicalTrial@acrivon.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arm 1: Anti-tumor activity of ACR-368 in Endometrial cancer subjects that are OncoSignature Positive. (time frame: Response will be assessed every 8 weeks from baseline through 2 years or death.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.