IvoLoC Trial: A Phase II Trial Evaluating the Efficacy of Ivonescimab in Metastatic Endocrine Refractory HR-positive HER2-negative or Triple Negative Invasive Lobular Carcinoma
IvoLoC Trial: A Phase II Trial Evaluating the Efficacy of Ivonescimab in Metastatic Endocrine Refractory HR-positive HER2-negative or Triple Negative Invasive Lobular Carcinoma
To learn if ivonescimab can help to control endocrine-refractory HR+ HER2- and/or TN mILC.
Primary Objectives To evaluate the 6-month PFS of ivonescimab in endocrine-refractory HR+ HER2- or Triple Negative (TN) mILC
Secondary Objectives
Exploratory Objectives:
Inclusion Criteria:
18 years of age or older.
Historically confirmed invasive lobular cancer with negative E-cadherin staining by IHC.
Estrogen receptor (ER) positive (>1%) or negative, progesterone receptor (PgR) positive or negative, and HER2-negative according to HER2 testing guidelines from the American Society of Clinical Oncology/College of American Pathologists.
Participants must be willing to undergo biopsy as required by the study if the tumor is safely accessible.
If ER+, participant must be endocrine refractory as per the treating oncologist assessment and has been exposed to at least one line of endocrine therapy prior to enrollment.
Participants who received prior chemotherapy, antibody-drug conjugates (ADCs), mTOR inhibitor and/or PI3K are eligible.
o Participants should not have received more than 2 chemotherapeutic agents and/or ADCs in the metastatic setting.
Eastern Cooperative Oncology Group Performance status ≤ 1.
Participant has either measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1 criteria OR at least one predominantly lytic bone lesion must be present.
Adequate Organ Function:
Creatinine clearance (CrCL) ≥ 60 mL/min using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥60 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (adjustment by BSA is not required for eGFR). CrCL or eGFR can be determined using the calculator from the National Kidney Foundation website (www.kidney.org).
Urine protein < 2+ or 24 hour urine protein quantification < 1.0 g
Liver:
i. Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; For participants with liver metastases, AST and ALT ≤ 5 × ULN
Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy or prophylactic coagulation). This applies only to patients who are not on therapeutic anti-coagulation. Participants receiving therapeutic anti-coagulation should be on a stable dose.
Participants with active hepatitis B are required to have stable or declining levels of hepatitis B DNA by polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for one month prior to enrolment on study.
All participants with active hepatitis C (hepatitis C virus [HCV] antibody positive with HCV RNA levels above the lower limit of detection) are excluded.
Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone
≤ 10 mg daily or equivalent)
Participants with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
The effects of ivonescimab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:
Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Participant/Partner post vasectomy, Implantable or injectable.
contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Exclusion Criteria:
Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study.
Participants who are receiving any other investigational agents.
Major surgical procedures or serious trauma within 4 weeks prior to treatment start date 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 enrolment.
Participants with symptomatic CNS metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to enrolment potential need for CNS radiation within the first cycle, or leptomeningeal disease.
History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrolment on study, including but not limited to:
Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
Live vaccine or live attenuated vaccine within 4 weeks prior to planned enrolment on study, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period.
Inactivated vaccines are permitted.
Participants managed with indwelling catheters (eg, PleurX) are allowed.
History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease
Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
Active autoimmune or lung disease requiring systemic therapy (eg, with disease modifying drugs, prednisone >10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to enrolment, however the following will be allowed:
History of major diseases before enrolment on study, specifically:
Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior tto enrolment on study, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)
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 enrolment
History of any grade arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrolment.
Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrolment.
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 enrolment.
Imaging during the screening period shows that the patient has:
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
Participants with psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because ivonescimab is an anti-cancer agent with the potential for teratogenic or abortifacient effects.
Participant is breastfeeding or plans to breastfeed during the study
Known allergy to any component of any study drug
Known history of severe hypersensitivity to other monoclonal antibodies
History or current evidence of any condition (medical [including adverse events from prior anticancer therapy, disorders secondary to tumor], surgical or psychiatric [including substance abuse]), or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, might lead to higher medical risk and/or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
jamouabbi@mdanderson.org(713) 792-7676