Study of Naxitamab and Sacituzumab Govitecan in Patients With Metastatic Triple-negative Breast Cancer (TNBC)

• 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.
• 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.
• Exploratory/Correlative Objectives • Investigate potential resistance mechanisms to naxitamab and develop a pre-clinical rationale for future therapeutic strategies.

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:

• 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.