Naxitamab plus sacituzumab govitecan for metastatic triple-negative breast cancer

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

This trial will test whether combining naxitamab with sacituzumab govitecan helps adults with metastatic triple-negative breast cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: sacituzumab, naxitamab, chemotherapy, prednisone
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT07011654 on ClinicalTrials.gov

What this trial studies

This Phase I/II trial combines naxitamab (an anti-GD2 monoclonal antibody) with sacituzumab govitecan (a Trop-2 antibody-drug conjugate) to treat adults with metastatic TNBC. Phase I will determine safety, tolerability, and the maximum tolerated dose/recommended Phase II dose (MTD/RP2D), and Phase II will measure objective response rate by RECIST v1.1 at the selected dose. Secondary endpoints include duration of response, progression-free survival, overall survival, and identification of GD2-related biomarkers of response or resistance. Participants must have received prior systemic therapy for metastatic disease, have measurable disease, adequate organ function, and be willing to provide tumor tissue for correlative studies.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed metastatic triple-negative breast cancer who have received at least one prior line of systemic chemotherapy for metastatic disease, have measurable disease, adequate organ and marrow function, and meet the study ECOG performance status criteria (0–1 for phase I, 0–2 for phase II).

Not a fit: Patients with poor performance status (ECOG >2), inadequate organ or marrow function, no measurable disease, or who cannot receive sacituzumab govitecan per standard care are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could increase response rates and prolong disease control for some patients with metastatic TNBC.

How similar studies have performed: Sacituzumab govitecan is an approved active therapy in metastatic TNBC and anti-GD2 antibodies have shown activity in other cancers, but combining naxitamab with sacituzumab govitecan for TNBC is a novel approach with limited prior clinical data.

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.

Where this trial is running

Houston, Texas

• The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Clinton Yam, MD — M.D. Anderson Cancer Center
• Study coordinator: Akshara S Raghavendra

Conditions Metastatic Triple-Negative Breast Cancer