Fox Chase Cancer Center | Philadelphia, PA
Status and phase
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About
This is an open label Phase 1b/2 study to evaluate the efficacy and safety of ACR-368 as monotherapy or in combination with ultralow dose gemcitabine in participants with platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma based on Acrivon's OncoSignature® test status.
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.
Enrollment
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Volunteers
Inclusion and exclusion 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:
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:
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.
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:
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:
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:
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:
For Endometrial Adenocarcinoma:
For Urothelial Carcinoma:
Primary purpose
Allocation
Interventional model
Masking
390 participants in 2 patient groups
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Central trial contact
Jean-Marie Cuillerot, MD; Jeanie Tang
Data sourced from clinicaltrials.gov
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