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

M.D. Anderson Cancer Center

Status and phase: Begins enrollment in 4 months; Phase 2; Phase 1

Conditions: Metastatic Triple-Negative Breast Cancer

Treatments: Drug: Naxitamab; Drug: Sacituzumab govitecan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07011654

2025-0438

NCI-2025-03798 (Other Identifier)

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 31 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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31 participants in 1 patient group

Treatment with Naxitamab and Sacituzumab Govitecan IV Q3W

Experimental group

Description:

Patients receive naxitamab IV on days 2, 4, and 6 of cycles 1-8 and sacituzumab govitecan IV days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: Sacituzumab govitecan

Drug: Naxitamab