A Phase 2 Study of ACR-368 in Endometrial Adenocarcinoma
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
- Endometrial Adenocarcinoma
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
Arm | Description | Assigned 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. |
|
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. |
|
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. |
|
Recruiting Locations
Phoenix, Arizona 85016
Theresa Thomas
Tucson, Arizona 85711
Stacey Kimbell
Little Rock, Arkansas 72205
Maroof Zafar
Duarte, California 91010
Lorna Rodriguez, MD
La Jolla, California 92037
Linda Nguyen
Los Angeles, California 90048
Victoria Arman
Newport Beach, California 92663
Esmerelda Martinez
Palo Alto, California 94304
Mohsin Rangwala
Sacramento, California 95817
Apinya Vorasaph
Santa Monica, California 90404
Rosa Vazquez
Aurora, Colorado 80045
Amelia Hardeman
Fort Myers, Florida 33905
Samith Sandadi
Miami Beach, Florida 33140
Evelyn Goya
Atlanta, Georgia 30322
Wilena Session
Gainesville, Georgia 30501
Trena Davis
Chicago, Illinois 60611
Peter Wojtowicz
Chicago, Illinois 60612
Hilda Diaz
Chicago, Illinois 60637
Amber Kindt
Urbana, Illinois 61801
Kendrith Rowland
Iowa City, Iowa 52252
Heidi Haugland
New Orleans, Louisiana 70112
Alexander Yates
Shreveport, Louisiana 71103
Amanda Maranto
Bethesda, Maryland 20892
Ann McCoy, RN
Silver Spring, Maryland 20910
Sujana Lalagari
Boston, Massachusetts 02115
Eleanor Estes
Worcester, Massachusetts 01605
Dawn Pepka-Jones
Detroit, Michigan 48201
Robert Morris, MD, PhD
Kansas City, Missouri 64132
Megan Werner
Hackensack, New Jersey 07601
Lori Cappello, MSN, APN-C, CCRP
New Brunswick, New Jersey 08903
Karen Jackson
New York, New York 10016
Karen Estok
New York, New York 10032
Reena Vattakalam
New York, New York 10065
Chrisann Kyi, MD
New York, New York 10128
Neha Kumarley
Rochester, New York 14642
Kelly Mateer
Pinehurst, North Carolina 28374
Pamela Mason
Centerville, Ohio 45459
Rebecca Wirth
Cincinnati, Ohio 45267
Bonny Lami
Hilliard, Ohio 43026
Kendall Lewis
Oklahoma City, Oklahoma 73104
Eugene, Oregon 97401
Cara Ratkovich
Portland, Oregon 97239
Yuki Bean
Pittsburg, Pennsylvania 15224
Siobhan Guyach
Sioux Falls, South Dakota 57104
Ashley Johnson
Dallas, Texas 75390
Annette Paulsen
Fort Worth, Texas 76104
Lynora Sullivan
Houston, Texas 77030
Anjali Raina
Salt Lake City, Utah 84112
Celine Saenz
Charlottesville, Virginia 22903
Alfredo Villalobos-Perez
Richmond, Virginia 23298
Melanie Hamilton
Seattle, Washington 98104
Thao Amy Nguyen
Seattle, Washington 98109
Patrick Panlasigui
Spokane, Washington 99204
Jodie Mactagone
Vancouver, Washington 98684
Margaret Bigler
Milwaukee, Wisconsin 53226
Subarna Paul
More Details
- NCT ID
- NCT05548296
- Status
- Recruiting
- Sponsor
- Acrivon Therapeutics
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.