RECRUITING

A Study of Ivonescimab in People With Endometrial and Cervical Cancers

Conditions

Endometrial Cancer Cervical Cancer Ivonescimab 25-007

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The researchers are doing this study to find out if ivonescimab is an effective treatment for people with endometrial cancer (EC) and/or cervical cancer (CC). The researchers will also look at whether the study drug is safe and causes few or mild side effects in participants.

Official Title

A Phase 2 Study of Ivonescimab (Bispecific Antibody Against PD1 and VEGF) For the Treatment of Endometrial (EC) and Cervical (CC) Cancers

Quick Facts

Study Start:2025-04-04

Study Completion:2027-04-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06925724

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically confirmed metastatic/recurrent endometrial or cervical cancer that has progressed after treatment with at least one platinum-based regimen. 1. Endometrial cancer histologies can include: endometrioid, serous, clear cell, dedifferentiated/undifferentiated, mixed epithelial, adenocarcinoma NOS, and carcinosarcoma. 2. Cervical cancer histologies can include: squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma * Measurable disease per RECIST v 1.1 criteria * Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2. * All patients must have received at least 1 line of platinum-based therapy. Prior PD1 or VEGF therapy is allowed. * Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤160/90 mmHg. * Have adequate laboratory values as defined in the following table: * Hematologic * Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 × 103/µL) * Platelets ≥100,000/µL * Hemoglobin ≥9.0 g/dL * International Normalized Ratio (INR) ≤1.5 * Renal * Creatinine clearance (CrCL) Urinalysis Creatinine clearance (CrCl) ≥ 50 mL/min using the Cockcroft-Gault formula * Urinalysis Urine protein \< 2+ (or 24 hour urine protein quantification \< 1.0 g) * Hepatic * Total bilirubin ≤1.5 ×ULN (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled) * AST and ALT ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) * TSH TSH within normal limits. If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal free T4 level is required. * Coagulation Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy, or prophylactic coagulation * Age ≥18 years at the time of informed consent. * Patients with treated brain metastases are eligible if follow-up brain imaging after CNS directed therapy shows no evidence of progression. Patients with treated brain metastasis should be excluded if they have any evidence of bleeding, or if they have large lesions at risk of bleeding ie \>1.5cm. Patients should also be off corticosteroids at the time of enrollment. Patients with untreated brain metastasis are excluded. * Not Pregnant and Not Nursing. If with childbearing potential, should have a negative urine pregnancy test at the time of screening. * Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 120 days after the last dose of the ivonescimab. * Must have clinical IMPACT data available, if data is not available, must have adequate tissue to available for clinical IMPACT. Patient will consent to 12-245 at enrollment if not previously completed. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.	* Major surgical procedures or serious trauma within 4 weeks prior to enrollment or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to enrollment. * Patient not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy. * History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to: 1. Gastrointestinal bleeding 2. Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed. 3. Nasal bleeding /epistaxis (bloody nasal discharge is allowed) 4. Need for therapeutic anticoagulant therapy within 14 days prior to enrollment. Note: Prophylactic anticoagulation for DVT/PE or to maintain venous patency is allowed. * History of major diseases before enrollment, specifically: 1. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or vascular disease that required hospitalization within 12 months prior to enrollment, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia) 2. History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before enrollment. 3. History of arterial thromboembolic event, venous thromboembolic event, , transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to enrollment. 4. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment 5. History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollmen * Imaging during the screening period shows that the patient has: 1. Radiologically documented evidence of major blood vessel invasion or encasement by cancer 2. Radiographic evidence of intratumor cavitation * Has participated in a study of an investigational agent and received cancer directed study therapy within 4 weeks prior to start of study treatment * Prolongation of QTc interval to \>480 msec * Active/Acute Hepatitis B infection * Active/Acute Hepatitis C infection * Known intolerance to either of the study drugs (or any of the excipients) * History of organ allograft (subject has had an allogenic tissue/solid organ transplant) * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 10 mg/d of prednisone or equivalent) may be approved after consultation with the study PI or Co-PI. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment * Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis * Patient with any prior immune related events (irAE) Grade 3 or higher that resulted in discontinuing or significant delay of dosing of immunotherapy * Has received a live-virus vaccination within 30 days of planned treatment start.

Inclusion Criteria

Exclusion Criteria

* Histologically confirmed metastatic/recurrent endometrial or cervical cancer that has progressed after treatment with at least one platinum-based regimen.
1. Endometrial cancer histologies can include: endometrioid, serous, clear cell, dedifferentiated/undifferentiated, mixed epithelial, adenocarcinoma NOS, and carcinosarcoma.
2. Cervical cancer histologies can include: squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma
* Measurable disease per RECIST v 1.1 criteria
* Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
* All patients must have received at least 1 line of platinum-based therapy. Prior PD1 or VEGF therapy is allowed.
* Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤160/90 mmHg.
* Have adequate laboratory values as defined in the following table:
* Hematologic
* Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 × 103/µL)
* Platelets ≥100,000/µL
* Hemoglobin ≥9.0 g/dL
* International Normalized Ratio (INR) ≤1.5
* Renal
* Creatinine clearance (CrCL) Urinalysis Creatinine clearance (CrCl) ≥ 50 mL/min using the Cockcroft-Gault formula
* Urinalysis Urine protein \< 2+ (or 24 hour urine protein quantification \< 1.0 g)
* Hepatic
* Total bilirubin ≤1.5 ×ULN (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
* AST and ALT ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
* TSH TSH within normal limits. If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal free T4 level is required.
* Coagulation Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy, or prophylactic coagulation
* Age ≥18 years at the time of informed consent.
* Patients with treated brain metastases are eligible if follow-up brain imaging after CNS directed therapy shows no evidence of progression. Patients with treated brain metastasis should be excluded if they have any evidence of bleeding, or if they have large lesions at risk of bleeding ie \>1.5cm. Patients should also be off corticosteroids at the time of enrollment. Patients with untreated brain metastasis are excluded.
* Not Pregnant and Not Nursing. If with childbearing potential, should have a negative urine pregnancy test at the time of screening.
* Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 120 days after the last dose of the ivonescimab.
* Must have clinical IMPACT data available, if data is not available, must have adequate tissue to available for clinical IMPACT. Patient will consent to 12-245 at enrollment if not previously completed.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

* Major surgical procedures or serious trauma within 4 weeks prior to enrollment or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to enrollment.
* Patient not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
* History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to:
1. Gastrointestinal bleeding
2. Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed.
3. Nasal bleeding /epistaxis (bloody nasal discharge is allowed)
4. Need for therapeutic anticoagulant therapy within 14 days prior to enrollment. Note: Prophylactic anticoagulation for DVT/PE or to maintain venous patency is allowed.
* History of major diseases before enrollment, specifically:
1. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or vascular disease that required hospitalization within 12 months prior to enrollment, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)
2. History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before enrollment.
3. History of arterial thromboembolic event, venous thromboembolic event, , transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to enrollment.
4. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment
5. History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollmen
* Imaging during the screening period shows that the patient has:
1. Radiologically documented evidence of major blood vessel invasion or encasement by cancer
2. Radiographic evidence of intratumor cavitation
* Has participated in a study of an investigational agent and received cancer directed study therapy within 4 weeks prior to start of study treatment
* Prolongation of QTc interval to \>480 msec
* Active/Acute Hepatitis B infection
* Active/Acute Hepatitis C infection
* Known intolerance to either of the study drugs (or any of the excipients)
* History of organ allograft (subject has had an allogenic tissue/solid organ transplant)
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 10 mg/d of prednisone or equivalent) may be approved after consultation with the study PI or Co-PI.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
* Patient with any prior immune related events (irAE) Grade 3 or higher that resulted in discontinuing or significant delay of dosing of immunotherapy
* Has received a live-virus vaccination within 30 days of planned treatment start.

Contacts and Locations

Study Contact

Maria Rubinstein, MD

CONTACT

646-888-6954

medgmoclinicaltrials@mskcc.org

Vicky Makker, MD

CONTACT

646-888-4224

medgmoclinicaltrials@mskcc.org

Principal Investigator

Maria Rubinstein, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk- Commack (All Protocol Activities)

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Maria Rubinstein, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-04-04

Study Completion Date2027-04-04

Study Record Updates

Study Start Date2025-04-04

Study Completion Date2027-04-04

Terms related to this study

Keywords Provided by Researchers

Ivonescimab
25-007

Additional Relevant MeSH Terms

Endometrial Cancer
Cervical Cancer