Testing Different Amounts of the Combination of Drugs M1774 and ZEN-3694 for the Treatment of Recurrent Ovarian and Endometrial Cancer

Recruiting now · Phase 1

Conditions studied: Recurrent Endometrial Carcinoma, Recurrent Endometrial Clear Cell Adenocarcinoma, Recurrent Endometrial Endometrioid Adenocarcinoma, Recurrent Endometrial Low Grade Endometrioid Adenocarcinoma, Recurrent Ovarian Clear Cell Adenocarcinoma, Recurrent Ovarian Endometrioid Adenocarcinoma, Recurrent Ovarian High Grade Serous Adenocarcinoma, Recurrent Ovarian Low Grade Endometrioid Adenocarcinoma, Recurrent Platinum-Resistant Ovarian Carcinoma

In brief

This phase Ib trial tests the safety, side effects, and best dose of M1774 when given with ZEN-3694 in treating patients with ovarian and endometrial cancer that has come back (recurrent). M1774 and ZEN-3694 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. M1774 and ZEN-3694 combined together has demonstrated to be better than either drug alone in killing ovarian tumor cells.

Key facts

Study ID

NCT05950464

Run by

National Cancer Institute (NCI)

People needed

65

Starts

2023-12-18

Expected to finish

2027-06-30

Last updated by the study team

2026-07-09

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have pathologically confirmed:
• PART I: Recurrent clear cell or endometrioid ovarian carcinoma (at least 50% morphology of clear cell and endometrioid required), recurrent clear cell and low grade endometrioid endometrial carcinoma (The International Federation of Gynecology and Obstetrics [FIGO] grade 1), or recurrent platinum resistant high grade serous ovarian carcinoma
• NOTE: platinum-resistant disease is defined as progression within < 6 months from completion of platinum-based therapy. The date should be calculated from the last administered dose of platinum therapy
• NOTE: Institutional pathology reports must be provided indicating at least 50% endometrioid or clear cell morphology for ovarian cancer.
• NOTE: Patients with recurrent endometrial carcinoma must not be eligible for or decline treatment with curative intent.
• PART II: Recurrent clear cell or endometrioid ovarian carcinoma (at least 50% tumor morphology of clear cell and endometrioid required). Recurrent clear cell or FIGO Grade 1 endometrioid endometrial carcinoma. Next Generation Sequencing (NGS) by Clinical Laboratory Improvement Act (CLIA) approved lab required for ARID1A status. Tumor will be determined as ARID1A pathologic alteration or likely pathologic alteration (Cohort I) or ARID1A wildtype by NGS (Cohort II). The number of patients in PART II cohort with clear cell or endometrioid EMCA will be capped at 33% (5 patients per cohort). Institutional pathology reports must be provided indicating at least 50% endometrioid or clear cell morphology for ovarian cancer.
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2
• Prior Treatment
• 1-3 prior cytotoxic therapies
• NOTE: For platinum-resistant HGSOC (PART 1) may have received up to 3 prior cytotoxic therapies after developing platinum resistant disease.
• Subjects with microsatellite instability- high (MSI-H) and/or mismatch repair protein deficient (dMMR) endometrioid endometrial cancer must have previously received an immune checkpoint inhibitor.
• Unlimited prior hormonal therapy, targeted therapy (including immunotherapy), and/or antiangiogenic therapy will be permitted.
• Washout periods (due to risk of myelosuppression):
• Cytotoxic chemotherapy - 3 weeks.
• Radiation therapy - 2 weeks (NOTE: patients with radiation to > 25% of the bone marrow are NOT eligible).
• Disease status:
• For PART I, evaluable disease or measurable disease required. NOTE: evaluable disease: defined as disease related abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions.
• For PART II, measurable disease by RECIST 1.1 is required. Patients will be required to undergo biopsy, which may be a non-target lesion but should not be the only RECIST measurable lesion.
• NOTE: Patients for PART II are required to undergo paired tumor biopsies. If at time of biopsy the biopsy is deemed unsafe by interventional radiology or attempted and is unsuccessful, patients may still enroll.
• Hemoglobin >= 9 g/dL (in the absence of transfusion within 28 days prior to dosing)
• Absolute neutrophil count >= 1,500 cells/mm\^3
• Platelet count >= 100,000 cells/mm\^3
• Calculated creatinine clearance (CrCL) of >= 50 mL/min by the Cockcroft-Gault formula
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled)

You may not qualify if…

• Patients who are receiving any other investigational agents.
• Patients who have received prior ATR, ATM, CHK, BET, EZH2, and/or PI3K inhibitors.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or M1774 used in study.
• Patients taking proton pump inhibitors given decreased solubility of M1774 with increased pH. Proton pump inhibitors must be discontinued 7 days prior to initiating the trial.
• Patients with corrected QT (QTc) over 450msec that does not correct with correction of electrolyte abnormalities or family history of long QT syndrome.
• Patients with severe, active co-morbidity defined as follows:
• No active infection requiring parenteral antibiotics.
• Known hereditary diseases characterized by genetic defects of DNA repair mechanisms, including ataxia telangiectasia, Nijmegen breakage syndrome, Werner syndrome, Bloom Syndrome, Fanconi anemia, xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy.
• Pregnant and breastfeeding women are excluded from this study because ZEN003694 has the potential for teratogenic or abortifacient effects and M1774 is genotoxic in in vivo nonclinical studies. Patients who discontinue breastfeeding are eligible for enrollment and may not resume breastfeeding until 1 month off treatment.
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694. Moderate inhibitors of CYP3A4 should be avoided. If alternative is not available, the use of moderate CYP3A4 inhibitors is permitted with careful monitoring and approval by study team. At the discretion of the provider, additional monitoring (labs, toxicity checks) may be implemented for use of moderate CYP3A4 inhibitors. Substrates of CYP1A2 with narrow therapeutic window also must be avoided white taking ZEN003694. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
• Patients receiving any medications or substances that are Factor Xa inhibitors are discouraged given concerns for thrombocytopenia (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed. If patients are not willing to switch to low molecular heparin, they must obtain approval by study team.
• Serious gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, presence of drainage gastrostomy tube, other chronic gastrointestinal disease, and/or other situations that may preclude absorption of oral medications M1774 and/or ZEN003694.
• M1774 restrictions:
• Patients who cannot discontinue drugs that are strong inhibitors of CYP3A4 or CYP1A2.
• Patients who cannot discontinue drugs that use hMATE1 or hMATE2-K substrates.

Where it is running

• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (enrolling)
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States (enrolling)
• University of Iowa/Holden Comprehensive Cancer Center — Iowa City, Iowa, United States (enrolling)
• University of Pennsylvania/Abramson Cancer Center — Philadelphia, Pennsylvania, United States (enrolling)
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States (enrolling)
• Women and Infants Hospital — Providence, Rhode Island, United States (enrolling)
• University of New Mexico Cancer Center — Albuquerque, New Mexico, United States (enrolling)
• Cleveland Clinic Foundation — Cleveland, Ohio, United States (enrolling)
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (enrolling)
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States (enrolling)
• NRG Oncology — Philadelphia, Pennsylvania, United States (enrolling)
• Wayne State University/Karmanos Cancer Institute — Detroit, Michigan, United States
• Augusta University Medical Center — Augusta, Georgia, United States
• Case Western Reserve University — Cleveland, Ohio, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.