Naxitamab and Sacituzumab Govitecan for the Treatment of Metastatic Triple-Negative Breast Cancer

Inclusion Criteria

• Patients must be 18 years or older and able to understand and give written informed consent * Note: Due to limited data on safety of naxitamab in patients > 65 years of age, enrollment of patients > 65 should only be done in select cases and after close discussion between the principal investigator (PI) and treating physician
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Life expectancy ≥ 3 months
• Histologically confirmed metastatic TNBC. (Estrogen receptor [ER] ≤ 10%; progesterone receptor [PgR] ≤ 10%, human epidermal growth factor receptor 2 [HER2]-negative as per American Society of Clinical Oncology [ASCO]/ College of American Pathologists [CAP] guidelines)
• Willingness to provide archival tumor tissue for correlative studies associated with this trial
• Patients should have received at least 1 prior line of systemic chemotherapy for metastatic TNBC and/or meet criteria to receive SG as standard of care
• Patients must have measurable disease by CT or MRI as per RECIST version 1.1 criteria as evaluated locally. Tumor lesions situated in a previously irradiated area are considered measurable if unequivocal progression has been documented in such lesions since radiation
• Patients must have recovered from adverse events due to previously administered systemic therapy or radiotherapy to less than or equal to grade 1 or baseline at the time of study entry * Note: The following are an exception to this criterion ** Any grade alopecia ** Grade 2 or lower neuropathy ** Grade 2 or lower immune-mediated endocrinopathies due to immunotherapy
• Recovered from major surgery for ≥ 2 weeks
• Absolute neutrophil count ≥ 1,500/uL
• Platelets ≥ 100,000/uL
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN; ≤ 5 x institutional ULN if known liver metastases
• Serum albumin > 3g/dL
• International normalized ratio (INR)/prothrombin time (PT) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 ULN unless patient is currently receiving therapeutic anticoagulant therapy
• Creatinine clearance ≥ 60 ml/min as assessed by the Cockcroft-Gault equation
• The effects of naxitamab in combination with sacituzumab govitecan on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and at least 35 days from the last study treatment. This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months) * History of hysterectomy or bilateral salpingo-oophorectomy * Ovarian failure (follicle stimulating hormone and estradiol in menopausal range, who have received whole pelvic radiation therapy) * History of bilateral tubal ligation or another surgical sterilization procedure * 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, subject/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
• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of naxitamab in combination with sacituzumab govitecan administration

Exclusion Criteria

• Positive serum pregnancy test or women who are lactating
• Known or severe (≥ grade 3) hypersensitivity or allergy to naxitamab and/or SG, their metabolites, or formulation excipient
• Have previously received treatment with an anti-GD2 antibody
• Have previously received topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor
• Have an active second malignancy * Note: Patients with a history of active cancer for 3 years prior to enrollment, or patients with surgically cured tumors with low risk of recurrence (e.g., nonmelanoma skin cancer, histologically confirmed complete excision of carcinoma in situ, or similar) are allowed to enroll
• Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Note: Patients with previously treated brain metastases may participate (with the exception of those treated with chemotherapy) provided they have stable CNS disease (defined as radiographic stability demonstrated with a minimum of 2 post-treatment brain imaging assessments; one performed during screening) for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and have also been clinically stable for at least 2 weeks while taking ≤ 10 mg/day of prednisone or its equivalent. All patients with carcinomatous meningitis are excluded regardless of clinical stability
• Have undergone an allogenic tissue or solid organ transplant
• Severe hypotension
• Meet any of the following criteria for cardiac disease * Myocardial infarction or unstable angina pectoris within 6 months of enrollment * History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation * New York Heart Association class III or greater congestive heart failure or known left ventricular ejection fraction of < 50% within 6 months prior to enrollment * Clinically significant cardiomyopathy * Clinically significant coronary artery disease
• Have inadequate pulmonary function, defined as one or more of the following: * Evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement * Room air pulse oximetry < 90% and/or abnormal pulmonary function tests if these assessments are clinically indicated
• Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal (GI) perforation within 6 months of enrollment
• Have uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure event within 3 months prior to enrollment)
• Have active serious infection requiring systemic antimicrobial therapy
• Patients positive for HIV-1 or 2 with a history of Kaposi sarcoma and/or Multicentric Castleman disease
• Have active hepatitis B virus (HBV) (defined as having a positive hepatitis B surface antigen [HBsAg] test) or hepatitis C virus (HCV) * For patients with a history of HBV infection, a hepatitis B core antibody test should be conducted at screening. If positive, hepatitis B deoxyribonucleic acid (DNA) testing will be performed and if active HBV infection is ruled out, the patient may be eligible * Patients who are HCV antibody positive with undetectable HCV viral load may be eligible
• Have other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations
• Has a diagnosis of immunodeficiency or receiving systemic corticosteroid therapy (higher than physiologic doses) ≥ 10 mg of prednisone per day or equivalent] or any other form of immunosuppressive therapy within 14 days of initiation of study treatment
• Has received prior radiotherapy within 1 weeks of start of study intervention