study of naxitamab and sacituzumab govitecan in patients with metastatic triple-negative breast cancer (tnbc)

Conditions: Metastatic Triple-Negative Breast Cancer

Summary: this phase i/ii trial tests the safety, best dose, and effectiveness of naxitamab in combination with sacituzumab govitecan in treating patients with triple-negative breast cancer (tnbc) that has spread from where it first started (primary site) to other places in the body (metastatic).

1. primary objectives * to determine the safety and tolerability and establish the maximum tolerated dose/recommended phase 2 dose (mtd/rp2d) of the combination of naxitamab and sacituzumab govitecan in participant s with metastatic tnbc. * to determine the objective response rate (orr) of naxitamab in combination with sacituzumab govitecan per recist v1.1 criteria in participant s with metastatic tnbc at the mtd/rp2d. 2. secondary objectives * to determine the duration of response, progression-free survival, and overall survival for participant s with metastatic tnbc treated with the combination of naxitamab plus sg: * to identify gd2-related biomarkers of response and resistance to the combination of naxitamab and sacituzumab govitecan. 3. exploratory/correlative objectives • investigate potential resistance mechanisms to naxitamab and develop a pre-clinical rationale for future therapeutic strategies.

Eligibility criteria:
inclusion criteria * male and female participants aged 18 years or older and able to understand and give written informed consent * eastern cooperative oncology group (ecog) performance status score of 0 or 1 (for the phase i portion of the study) and ecog performance status of 0-2 (for the phase ii portion of the study) * life expectancy of at least 3 months * histologically confirmed metastatic tnbc. (estrogen receptor \[er\] ≤10%; progesterone receptor \[pgr\] ≤10%, her2-negative as per asco/cap guidelines) * willingness to provide archival tumor tissue for correlative studies associated with this trial. * received at least 1 prior line of systemic chemotherapy for metastatic tnbc and/or meet criteria to receive sacituzumab govitecan as standard of care * measurable disease by ct or mri as per recist version 1.1 criteria * adequate organ and marrow function as defined below: 2. exclusion criteria participants who meet any of the following exclusion criteria are not eligible to be enrolled in this study. * positive serum pregnancy test or women who are lactating. * known or severe (≥ grade 3) hypersensitivity or allergy to naxitamab and/or sacituzumab govitecan, their metabolites, or formulation excipient. * grade 3 or greater peripheral neuropathy * have previously received treatment with an anti-gd2 antibody * prior treatment with trop2-targeting antibody drug conjugates in the metastatic setting. participant s who have received trop2-targeting antibody drug conjugates in the neoadjuvant setting or adjuvant setting are eligible if at least 6 months have elapsed since the last dose of trop2-targeting antibody drug conjugate. * have an active second malignancy. participant s with a history of active cancer for 3 years prior to enrollment, or participant s with surgically cured tumors with low risk of recurrence (eg, 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. * have undergone an allogenic tissue or solid organ transplant. * uncontrolled hypertension, defined as a consistently elevated systolic blood pressure of \>160 mmhg despite optimal medical management * clinically significant cardiac disease * inadequate pulmonary function * active chronic inflammatory bowel disease (ulcerative colitis, crohn's disease) or gi perforation within 6 months of enrollment. * uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure event within 3 months prior to enrollment) * active serious infection requiring systemic antimicrobial therapy. * participants positive for hiv-1 or 2 with a history of kaposi sarcoma and/or multicentric castleman disease. * have active hepatitis b or c infection * 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.