Ovarian Cancer Clinical Trial

A Study of ACR-368 in Ovarian Carcinoma, Endometrial Adenocarcinoma, and Urothelial Carcinoma

Summary

This is an open label Phase 1b/2 study to evaluate the efficacy and safety of ACR-368 as monotherapy or in combination with low dose gemcitabine in participants with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma based on Acrivon's OncoSignature® test status.

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Full Description

Participants will be selected for predicted efficacy of ACR-368 using the OncoSignature® Companion Diagnostic test. Participants will be allocated to one of 2 arms based on OncoSignature result:

Arm 1: OncoSignature Positive tumors

Arm 2: OncoSignature Negative

Participants in Arm 1 will receive ACR-368 as monotherapy. Participants in Arm 2 will receive the combination of ACR-368 and ultralow-dose gemcitabine. Participants in both arms will be treated until disease progression, unacceptable toxicity or any criterion for stopping the study drug or withdrawal from the trial occurs.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criterial: General

Participant must be able to give signed, written informed consent.
Participant must have histologically confirmed, locally advanced (i.e., not amenable to curative surgery and/or radiation therapy) or metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.

Participant must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria (by local Investigator) (Eisenhauer, 2009).

Participant must have radiographic evidence of disease progression based on RECIST criteria following the most recent line of treatment. Biochemical recurrence (eg, CA-125 in ovarian carcinoma) only is not considered as disease progression.

Participant must be willing to provide tissue from a newly obtained tumor biopsy from an accessible tumor lesion not previously irradiated after signed informed consent.

Newly obtained is defined as a specimen obtained up to 6 weeks prior to initiation of treatment on Day 1 if no intercurrent systemic therapy in the interval.

Participant must be willing to provide an archival tumor tissue block or at least 20 unstained slides, if available.

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.

Participant must have adequate organ function at Screening, defined as:

Absolute neutrophil count > 1500 cells/µL without growth factor support within 1 week prior to obtaining the hematology values at Screening.
Hemoglobin ≥ 9.0 g/dL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at Screening.
Platelets ≥ 100,000 cells/µL without transfusion within 1 week prior to obtaining the hematology values at Screening.
Calculated creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft Gault formula.
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 (including if receiving anticoagulation therapy): Prothrombin time within 1.5 x ULN. Activated partial thromboplastin time within 1.5 x ULN. If the patient is anticoagulated, must be on a stable dose of anticoagulant for ≥ 1 month.

Tumor Specific Inclusion Criteria

For Ovarian Carcinoma:

Participant must have histologically documented, platinum resistant, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer. Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy, is eligible.

Platinum sensitive disease, defined as disease which progress after 6 or more months after the completion of platinum-based therapy and primary platinum refractory disease, defined as progression while on the upfront platinum-based therapy, is not eligible.

a. Carcinosarcoma is eligible.

Participant must have received at least 1 but no more than 6 prior lines of systemic therapy, including at least 1 line of therapy containing platinum derivative and taxane, and single-agent therapy must be appropriate as the next line of treatment:
Participant must have had prior bevacizumab or did not receive bevacizumab based on Investigator judgment (see Section 2.1.1).

For Endometrial Carcinoma

Participant must have histologically documented, high-grade endometrial adenocarcinoma.

All Grade 3 International Federation of Gynecology and Obstetrics epithelial endometrial histologies are eligible including: endometrioid, serous, and clear-cell carcinoma.
Carcinosarcoma is eligible. Enrollment of participants with this histology will be capped at 5% for each cohort.
Participant must have no more than 3 prior lines of therapy in the recurrent setting, including platinum-based chemotherapy for subtypes of endometrial adenocarcinoma where it is a standard of care.
Participant must have documented failure or ineligibility (based on Investigator judgement) for prior anti-programmed cell death protein 1/anti-programmed death- ligand 1 (PD 1/PD L1) based therapy for advanced/metastatic disease. Prior combination of PD 1/PD L1 inhibitor and vascular endothelial growth factor tyrosine kinase inhibitor is acceptable.

For Urothelial Carcinoma

Participant must have histologically documented, advanced (metastatic and/or unresectable) urothelial carcinoma. Variant histology is allowed as long as the tumor is predominantly urothelial.

Participants must have:

Received a platinum containing regimen (cisplatin or carboplatin) in the metastatic/locally advanced, neoadjuvant, or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting, participant must have progressed within 12 months of completion.
Failed or have been ineligible for checkpoint inhibitors (including PD-1 or PD-L1 inhibitors).
Failed or have been ineligible for enfortumab vedotin.
Have no known life-prolonging therapy available

Exclusion Criteria: General

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 had a failure to recover from the reversible effects of prior anti-cancer therapy, as follows:

Endocrine events from prior immunotherapy at Grade > 2.
Neuropathy events from prior cytotoxic therapies at Grade > 2.
All other reversible effects of prior anti- cancer therapy (except alopecia) at Grade >1 or Baseline.
Participant had systemic therapy or radiation therapy within 2 weeks prior to the first dose of study drug.
Participants has known human immunodeficiency virus, 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 (QTc) > 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 a history of bowel obstruction requiring decompression through a nasogastric tube within 8 weeks of Screening. Participants has signs or symptoms of intestinal obstruction, which include nausea, vomiting, and objective radiologic finding of bowel obstruction.
Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368

Tumor Specific Exclusion Criteria

For Ovarian Carcinoma:

Participant has non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma.
Participant has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis within 4 weeks of Screening. Participant has a planned therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing.
Participant has a history of active inflammatory bowel disease within 2 years prior to Screening.
Participant has a history of bowel perforation, fistula, necrosis, or leak within 8 weeks of Screening.

For Endometrial Adenocarcinoma:

Participant has low-grade endometrioid carcinoma.
Participant has mesenchymal tumors of the uterus.
Participant has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis within 4 weeks of Screening. Participant has a planned therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing.

For Urothelial Carcinoma:

Participant has sarcoma, carcinosarcoma, melanoma, or lymphoma of the bladder.
Participant has not received a previous platinum-based regimen.
Participant has small cell or neuroendocrine histology.

Study is for people with:

Ovarian Cancer

Phase:

Phase 1

Estimated Enrollment:

390

Study ID:

NCT05548296

Recruitment Status:

Recruiting

Sponsor:

Acrivon Therapeutics

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There are 68 Locations for this study

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University of South Alabama Mitchell Cancer Institute
Mobile Alabama, 36604, United States More Info
Stefanie White
Contact
Jennifer Scalici, MD
Principal Investigator
Alaska Women's Cancer Center
Anchorage Alaska, 99508, United States More Info
Katelyn Kammers
Contact
Melissa Hardesty, MD, MPH
Principal Investigator
HonorHealth
Phoenix Arizona, 85016, United States More Info
Theresa Thomas
Contact
Lyndsay Willmott, MD
Principal Investigator
Arizona Oncology Associate, PC- HOPE
Tucson Arizona, 85711, United States More Info
Stacey Kimball
Contact
Joseph Buscema, MD
Principal Investigator
University of Arkansas for Medical Sciences
Little Rock Arkansas, 72205, United States More Info
Maroof Zafar
Contact
Heather Williams, MD
Principal Investigator
City of Hope National Medical Center
Duarte California, 91010, United States More Info
Lorna Rodriguez, MD
Contact
Mihae Song, MD
Principal Investigator
UC San Diego Moores Cancer Center
La Jolla California, 92037, United States More Info
Madeline Kirkegaard
Contact
Alexandrea Cronin
Contact
Ramez Eskander, MD
Principal Investigator
USC/Norris Comprehensive Cancer Center
Los Angeles California, 90033, United States More Info
Kimberly Areieli
Contact
Koji Matsuo, MD
Principal Investigator
Cedars Sinai Medical Center
Los Angeles California, 90048, United States More Info
Victoria Arman
Contact
Garrett Crook
Contact
Bobbie Rimel, MD
Principal Investigator
Hoag Cancer Center
Newport Beach California, 92663, United States More Info
Esmerelda Martinez
Contact
Alberto Mendivil, MD
Principal Investigator
UC Irvine Health
Orange California, 92868, United States More Info
Dorothy Huttar
Contact
Nataliya Mar, MD
Principal Investigator
Stanford Cancer Center
Palo Alto California, 94304, United States More Info
Mohsin Rangwala
Contact
Ali Khaki, MD
Principal Investigator
University of California, Davis Comprehensive Cancer Center
Sacramento California, 95817, United States More Info
Tanya Khan
Contact
Hui Chen, MD
Principal Investigator
University of California Los Angeles (UCLA)
Santa Monica California, 90404, United States More Info
Rosa Vazquez
Contact
Alexandra Drakaki, MD
Principal Investigator
University of Colorado
Aurora Colorado, 80045, United States More Info
Tyler Poon
Contact
Lindsay Brubaker, MD
Principal Investigator
Yale Cancer Center
New Haven Connecticut, 06520, United States More Info
Ingrid Palma
Contact
Joseph W. Kim, MD
Principal Investigator
Florida Gynecologic Oncology/Regional Cancer Center
Fort Myers Florida, 33905, United States More Info
Samith Sandadi
Contact
Edward Grendys, MD
Principal Investigator
Mount Sinai Comprehensive Cancer Center
Miami Beach Florida, 33140, United States More Info
Ana Lacombe
Contact
Brian Slomovitz, MD
Principal Investigator
Emory University
Atlanta Georgia, 30322, United States More Info
Wilena Session
Contact
Mehmet Bilen, MD
Principal Investigator
Northeast Georgia Medical Center
Gainesville Georgia, 30501, United States More Info
Trena Davis
Contact
Chelsea K Chandler, MD
Principal Investigator
Northwestern Medicine
Chicago Illinois, 60611, United States More Info
Jack Burrows
Contact
Daniela Matei, MD
Principal Investigator
University of Illinois Cancer Center
Chicago Illinois, 60612, United States More Info
Mercedes Carrasquillo
Contact
Shannon MacLaughlan, MD
Principal Investigator
University of Chicago Medicine
Chicago Illinois, 60637, United States More Info
Katrina Cabrera
Contact
John Moroney, MD
Principal Investigator
Carle Cancer Center
Urbana Illinois, 61801, United States More Info
Kendrith Rowland
Contact
Pratima Chalasani, MD
Principal Investigator
University of Iowa
Iowa City Iowa, 52252, United States More Info
Heidi Haugland
Contact
Yousef Zakharia, MD
Principal Investigator
LSU Health Sciences
New Orleans Louisiana, 70112, United States More Info
Krystal Giddix
Contact
Amelia Jernigan, MD
Principal Investigator
Trials365, LLC
Shreveport Louisiana, 71103, United States More Info
Carrie Kay
Contact
Destin Black, MD
Principal Investigator
American Oncology Partners of Maryland PA
Bethesda Maryland, 20817, United States More Info
Natalie Bongiorno
Contact
Mark Goldstein, MD
Principal Investigator
National Institutes of Health, Clinical Center
Bethesda Maryland, 20892, United States More Info
Ann McCoy, RN
Contact
Jung-Min Lee, MD
Principal Investigator
Holy Cross Hospital
Silver Spring Maryland, 20910, United States More Info
Sujana Lalagari
Contact
James F Barter, MD
Principal Investigator
Dana Farber Cancer Institute
Boston Massachusetts, 02115, United States More Info
Hope Needham
Contact
Panagiotis Konstantinopoulos, MD, PhD
Principal Investigator
University of Massachusetts Chan Medical School
Worcester Massachusetts, 01605, United States More Info
Dawn Pepka-Jones
Contact
Cara Gregoire
Contact
Susan Zweizig, MD
Principal Investigator
Karmanos Cancer Institute
Detroit Michigan, 48201, United States More Info
Robert Morris, MD, PhD
Contact
Ira Winer, MD, PhD
Principal Investigator
HCA Midwest
Kansas City Missouri, 64132, United States More Info
Megan Werner
Contact
Kristopher LyBarger, DO
Principal Investigator
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack New Jersey, 07601, United States More Info
Lauren Wiest
Contact
Donna McNamara, MD
Principal Investigator
Rutgers Cancer Institute of NJ
New Brunswick New Jersey, 08903, United States More Info
Karen Jackson
Contact
Aliza Leiser, MD
Principal Investigator
Laura & Isaac Perlmutter Cancer Center
New York New York, 10016, United States More Info
Karen Estok
Contact
Bhavana Pothuri, MD
Principal Investigator
New York Presbyterian Hospital-Columbia University Medical Center
New York New York, 10032, United States More Info
Reena Vattakalam
Contact
June Hou, MD
Principal Investigator
Memorial Sloan-Kettering Cancer Center
New York New York, 10065, United States More Info
Chrisann Kyi, MD
Contact
Jonathan Rosenberg, MD
Principal Investigator
Mount Sinai Health System
New York New York, 10128, United States More Info
Neha Kumarley
Contact
Stephanie Blank, MD
Principal Investigator
University of Rochester Medical Center
Rochester New York, 14642, United States More Info
Stuart Fisher
Contact
Brendan Guercio, MD
Principal Investigator
University of North Carolina at Chapel Hill
Chapel Hill North Carolina, 27599, United States More Info
Tracy Rose, MD
Contact
Young Whang, MD
Contact
Matthew Milowsky, MD
Principal Investigator
FirstHealth of the Carolinas
Pinehurst North Carolina, 28374, United States More Info
Pamela Mason
Contact
Michael J. Sundborg, MD
Principal Investigator
Gabrail Cancer Center
Canton Ohio, 44718, United States More Info
Kim Roby
Contact
Nashat Gabrail, MD
Principal Investigator
Miami Valley Hospital South
Centerville Ohio, 45459, United States More Info
Rebecca Wirth
Contact
Michael Guy, MD
Principal Investigator
University of Cincinnati Cancer Center
Cincinnati Ohio, 45267, United States More Info
Margan Harris
Contact
Caroline Billingsley, MD
Principal Investigator
Cleveland Clinic Foundation
Cleveland Ohio, 44195, United States More Info
Timothy Gilligan
Contact
Moshe Ornstein
Contact
Shilpa Gupta, MD
Principal Investigator
Ohio State University
Hilliard Ohio, 43026, United States More Info
Lindsey Swavel
Contact
Kendall Lewis
Contact
David O'Malley, MD
Principal Investigator
Stephenson Cancer Center at OU Health
Oklahoma City Oklahoma, 73104, United States More Info
Debra Richardson, MD
Principal Investigator
Oncology Associates of Oregon
Eugene Oregon, 97401, United States More Info
Jeanne Schaffer
Contact
Charles Anderson, MD
Principal Investigator
Oregon Health & Sciences University
Portland Oregon, 97239, United States More Info
Yuki Bean
Contact
Christopher Ryan
Contact
Elizabeth Munro, MD
Principal Investigator
Fox Chase Cancer Center
Philadelphia Pennsylvania, 19111, United States More Info
Leslie Katona
Contact
Angela Jain, MD
Principal Investigator
West Penn Hospital
Pittsburgh Pennsylvania, 15224, United States More Info
Siobhan Guyach
Contact
Sarah Crafton, MD
Principal Investigator
Women & Infants Hospital
Providence Rhode Island, 02905, United States More Info
Cara Mathews, MD
Principal Investigator
Sanford Health
Sioux Falls South Dakota, 57104, United States More Info
Ashley Johnson
Contact
Maria Bell, MD
Principal Investigator
Texas Oncology-Dallas Presbyterian Hospital
Dallas Texas, 75231, United States More Info
Nancy Jones
Contact
Kristi J. McIntyre, MD
Principal Investigator
University of Texas Southwestern Medical Center
Dallas Texas, 75390, United States More Info
Annette Paulsen
Contact
David Miller, MD
Principal Investigator
Texas Oncology
Fort Worth Texas, 76104, United States More Info
Lynora Sullivan
Contact
Noelle Cloven, MD
Principal Investigator
University of Texas, MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Amanda Eckert
Contact
Funda Meric-Bernstam, MD
Principal Investigator
Huntsman Cancer Institute, University of Utah
Salt Lake City Utah, 84112, United States More Info
Celine Saenz
Contact
Theresa Werner, MD
Principal Investigator
University of Virginia Health System
Charlottesville Virginia, 22903, United States More Info
Jungeun Kim
Contact
Linda Duska, MD
Principal Investigator
Virginia Commonwealth University
Richmond Virginia, 23298, United States More Info
Melanie Hamilton
Contact
Leslie Randall, MD
Principal Investigator
Swedish Cancer Center
Seattle Washington, 98104, United States More Info
Amy Nguyen
Contact
Fernanda Musa, MD
Principal Investigator
Fred Hutchinson Cancer Center
Seattle Washington, 98109, United States More Info
Patrick Panlasigui
Contact
Petros Grivas, MD, PhD
Principal Investigator
Providence Sacred Heart Medical Center and Children's Hospital
Spokane Washington, 99204, United States More Info
Jodie Mactagone
Contact
Melanie Bergman, MD
Principal Investigator
Summit Cancer Center
Spokane Washington, 99208, United States More Info
Monika Chaudhry
Contact
Arvind Chaudhry, MD, PhD
Principal Investigator
Northwest Cancer Specialists, P.C.
Vancouver Washington, 98684, United States More Info
Dana Lassiter
Contact
Weiya Wysham, MD
Principal Investigator
Froedtert and Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States More Info
Subarna Paul
Contact
William Bradley, MD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Ovarian Cancer

Phase:

Phase 1

Estimated Enrollment:

390

Study ID:

NCT05548296

Recruitment Status:

Recruiting

Sponsor:


Acrivon Therapeutics

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