FMT in Triple Negative Breast Cancer Guided by ctDNA

Inclusion criteria

PHASE 1

• Patients must be 18 years old or older.
• Patients must have a confirmed diagnosis of TNBC (defined as estrogen receptor expression 0-10%, progesterone receptor expression 0-10%, and HER-2/neu negative (immunohistochemistry 0, 1+, or 2+ and fluorescent in-situ hybridization negative for HER-2 gene amplification) and are about to start neoadjuvant chemotherapy.
• Patients with ECOG performance of 0-2.
• Patients who are willing to provide serial stool and blood samples.
• Patients must be able to provide written informed consent
• Patients with available primary tumor biopsy tissue for molecular analysis

PHASE 2

• Patients must be 18 years old or older.
• Patients must have a confirmed diagnosis of TNBC (defined as estrogen receptor expression 0-10%, progesterone receptor expression 0-10%, and HER-2/neu negative (immunohistochemistry 0, 1+, or 2+ and fluorescent in-situ hybridization negative for HER-2 gene amplification) and are about to start neoadjuvant chemotherapy-immunotherapy.
• Patients with ECOG performance of 0-2.
• Patients must be able to provide written informed consent and understand the infectious risks associated with FMT administration.
• Ability to ingest capsules.
• Patients receiving systemic steroids at physiologic doses are permitted to enroll assuming steroid dose is not above the acceptable threshold (>10 mg prednisone daily or equivalent).

Exclusion criteria

PHASE 1

• Clinical or radiological evidence of metastatic disease.
• Known infection with HIV or hepatitis.
• Pregnant woman.

PHASE 2

• Previous anti-PD-1 treatment.
• Patient with a secondary malignancy.
• Pregnant or breastfeeding or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Current exposure to high-dose oral or intravenous corticosteroids (>10 mg of prednisone daily or equivalent). Patients who require intermittent use of bronchodilators or local steroid injections are not excluded from the study.
• Absolute neutrophil count <1.0 within 48 hours of planned FMT administration
• Has a diagnosis of immunodeficiency (for example, HIV or transplantation) or any other form of immunosuppressive therapy before trial treatment.
• Ongoing use of antibiotics or previous use of antibiotics one week before the FMT procedure.
• Probiotic supplements and food products labeled as containing probiotics must be discontinued a minimum of 24 hours before FMT administration and are not permitted during the course of neoadjuvant immunotherapy treatment.
• Presence of a chronic intestinal disease (for example, celiac, malabsorption, and colonic tumor).
• Presence of absolute contraindications to FMT administration, including toxic megacolon, severe dietary allergies (for example, shellfish, nuts, or seafood), and inflammatory bowel disease.
• Expected to require any other form of systemic or localized anti-neoplastic therapy other than those proposed by the study while on study.
• Has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo, type I diabetes, or resolved childhood asthma/atopy are exceptions to this rule.
• A history of recent (<30 days) (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has serious concomitant illnesses, such as uncontrolled cardiovascular disease (congestive heart failure, uncontrolled hypertension, active evidence of cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders. This includes HIV or AIDS-related illness or active hepatitis B or C virus.
• Has an active infection requiring systemic therapy.
• Patient has received a live vaccine within 4 weeks before the first dose of treatment. Note that seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (for example, FluMist) are live attenuated vaccines and are not allowed.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.