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Protocol Details

A Phase 1b/2 Basket Study of ACR-368 as Monotherapy and in Combination with Gemcitabine in Adult Subjects with Platinum-Resistant Ovarian Carcinoma, Endometrial Adenocarcinoma, and Urothelial Carcinoma Based on Acrivon Oncosignature(R) Status

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 120 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Bladder Cancer;
Urogenital Cancer

Recruitment Keyword(s)



Ovarian Cancer;
Endometrial Cancer;
Urothelial Cancer

Investigational Drug(s)


Investigational Device(s)



Drug: ACR-368
Drug: Gemcitabine
Device: OncoSignature

Supporting Site

National Cancer Institute


Carcinoma is a type of cancer that starts in cells that make up the skin or the tissue that lines organs and glands. These include cancers of the ovaries (ovarian carcinoma); the lining of the womb (endometrial adenocarcinoma); and the bladder (urothelial carcinoma). These cancers often return after the first round of treatment, and survival rates are very low. Better treatments are needed.


To test a study drug (ACR-368), used alone or combined with an approved drug (low dose gemcitabine, or LDG).


People aged 18 years and older who have ovarian, endometrial, or urothelial cancer.


Participants will be screened. They will have a physical exam and a test of heart function. They will give blood and urine samples. They will have an imaging scan. They will have a biopsy (tissue sample) of their tumor.

Participants will be assigned to 1 of 2 groups.

ACR-368 is administered intravenously, that is, through a tube attached to a needle inserted into a vein in the arm. Each treatment takes about 60 minutes. The drug will be given once every 14 days to all participants.

Participants in the second group will also receive LDG. LDG is also administered intravenously, over about 60 minutes. Every 14 days, these participants will receive the LDG first; then, after a 3-hour wait, they will receive the ACR-368.

Imaging scans, blood sampling, and other tests may also be done during treatment visits.

Participants may remain in the study as long as they are benefiting from treatment.

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-Subjects who are 18 years of age or older at time of consent.

-Subject must be able to give signed, written informed consent.

-Subject must have histologically confirmed, locally advanced (ie, not amenable to curative surgery and/or radiation therapy) or metastatic cancer that has progressed during or after at least 1 prior therapeutic regimen.

-Subject must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria (by local Investigator). Subject 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.

-Subject must be willing to provide tissue from a newly obtained tumor biopsy from an accessible tumor lesion not previously irradiated. Newly obtained is defined as a specimen obtained up to 12 weeks prior to initiation of treatment on Day 1 if no intercurrent systemic therapy in the interval. For biopsies obtained prior to the signing of the consent, Investigators should contact the Medical Monitor to confirm sample will be acceptable.

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

-Subject 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.

-Subject must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.

-Subject must have an estimated life expectancy of longer than 3 months.

-Subject must have adequate organ function at Screening, defined as:

--Absolute neutrophil count > 1500 cells/microliter 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/microliter without transfusion within 1 week prior to obtaining the hematology values at Screening.

--Calculated creatine clearance >= 30 mL/min as calculated by the Cockcroft-Gault formula.

--Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3 (SqrRoot) upper limit of normal (ULN); <= 5 x ULN if liver metastases are present.

--Total bilirubin <= 1.5 x ULN not associated with Gilbert s syndrome. If associated with Gilbert s syndrome <= 3 x ULN is acceptable.

--Serum albumin 3 g/dL.

-Subject 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 anticoagulant for >= 1 month:

--Prothrombin time within the ULN, and

--Activated partial thromboplastin time within the ULN.

-Female subjects must be non-lactating.

-Women of childbearing potential must agree to use a highly effective contraceptive method while on ACR-368 and for at least 3 months after the last dose. Males who have either a female partner of childbearing potential or a pregnant female partner must be sterile (biologically or surgically) or use a highly effective method of contraception (any combination of physical and chemical methods) while on ACR-368 and for at least 3 months after the last dose.

-WOCBP must have a negative pregnancy test prior to biopsy (if the biopsy is performed within the Screening window) and within 48 hours prior to dosing of study drug.


Ovarian Carcinoma:

-Subject must have histologically documented, 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. Subjects with platinum sensitive disease (defined as disease which progresses after 6 or more months after the completion of platinum-based therapy) and subjects with primary platinum-refractory disease (defined as progression while on the upfront platinum-based therapy) are not eligible

-Subject 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 singleagent therapy must be appropriate as the next line of treatment:

--Adjuvant +/- neoadjuvant is considered 1 line of therapy.

--Maintenance therapy (eg, bevacizumab or poly adenosine diphosphate-ribose polymerase [PARP] inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently).

--Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently).

-Subject must have had prior bevacizumab or did not receive bevacizumab based on Investigator judgment.

-Subjects with or without documented test results assessing alterations in the DNA repair pathway genes, eg, Breast Cancer gene 1 (BRCA1), BRCA2, and homologous recombination deficiency, at Screening are eligible. Patients with known BRCA mutated tumors should have received a PARP inhibitor maintenance or treatment.

-Subject will be enrolled regardless of tumoral folate receptor alpha expression status. Folate receptor alpha expression status will be collected for retrospective analysis, if the information is available.

Endometrial Adenocarcinoma:

-Subject 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 subjects with this histology will be capped at 5% for each cohort.

--Subject 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.

-Subject 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) immunotherapy as single agent or in combination with lenvatinib for advanced/metastatic disease. Prior combination of PD-1/PD-L1 inhibitor and vascular endothelial growth factor tyrosine kinase inhibitor is acceptable.

-Prior neoadjuvant or adjuvant chemotherapy included in initial treatment are not considered first- or later-line treatment unless such treatments were completed less than 6 months prior to the current tumor recurrence. Prior treatment may include chemotherapy, chemotherapy/radiation therapy, and/or consolidation/maintenance therapy.

-Prior treatment with hormonal therapy or inhibitors of the mTOR or CDK4/6 pathways are not considered a line of therapy in any setting.

Urothelial Carcinoma:

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

-Subjects 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, subject 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.


A subject will be excluded from the study if any of the following criteria apply:

-Subject with known symptomatic brain metastases requiring > 10 mg/day of prednisolone (or its equivalent). Subjects 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.

-Subject 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.

-Subject had systemic therapy or radiation therapy within 2 weeks prior to the first dose of study drug.

-Subjects has known human immunodeficiency virus, hepatitis B, or hepatitis C infection that is considered uncontrolled based on the criteria.

-Subject has a history of clinically meaningful coagulopathy, bleeding diathesis.

-Subject 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; unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction < 20%, transient ischemic attack, or cerebrovascular accident within 6 months of Day 1).

-Subject has a history of major surgery within 4 weeks of Screening.

-Subject has a history of bowel obstruction requiring decompression through a nasogastric tube within 8 weeks of Screening. Subjects has signs or symptoms of intestinal obstruction, which include nausea, vomiting, and objective radiologic finding of bowel obstruction.

-Subject has taken a prior cell cycle CHK1 inhibitor, including ACR-368.

-Women who are pregnant or lactating.

-Subject has a history of other malignancy within 2 years prior to enrollment. NOTE: Subjects with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix or breast) are eligible.


Ovarian Carcinoma:

-Subject has non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma.

-Subject has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis within 4 weeks of Screening.

-Subject has a history of active inflammatory bowel disease within 2 years prior to Screening.

-Subject has a history of bowel perforation, fistula, necrosis, or leak within 8 weeks of Screening.

Endometrial Adenocarcinoma:

-Subject has low-grade endometrioid carcinoma.

-Subject has mesenchymal tumors of the uterus.

-Subject has a history of clinically meaningful ascites, defined as a history of paracentesis or thoracentesis within 4 weeks of Screening.

Urothelial Carcinoma:

-Subject has sarcoma, carcinosarcoma, melanoma, or lymphoma of the bladder.

-Subject has not received a previous platinum-based regimen.

-Subject has small cell or neuroendocrine histology.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Jung-Min Lee, M.D.
National Cancer Institute (NCI)
(240) 760-6128

Ann C. McCoy, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 82
Room 233
9030 Old Georgetown Road
Bethesda, Maryland 20892
(240) 760-6021

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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