Phase II Trial of Pembrolizumab/Chemotherapy With Live Biotherapeutic Product MO-03 in Patients With Early Stage Triple Negative Breast Cancer

Inclusion criteria

• Female or male age ≥ 18 years of age.
• Patients with high-risk early stage triple negative breast cancer. Triple negative status will be defined as ER≤10%, PR≤10%, HER2 negative (by FISH) per ASCO-CAP guidelines.
• Clinically staging T1c any N M0 or any T N1-3 M0.
• Willing to provide FFPE from baseline standard of care biopsy and post-treatment residual tumor at the time of surgery.
• ECOG 0-1
• Patients must have adequate organ function as defined in the following. Specimens must be collected within 28 days prior to the start of study treatment.
• For patients who will receive regimen 1 only: Participants must have adequate cardiac function. Participants must have left ventricular ejection fraction ≥ 50% as assessed by either ECHO or MUGA within 28 days prior to the start of treatment. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better.
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test within 28 days of the start of treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Male participants: A male participant must agree to use a contraception as detailed in Appendix B of this protocol during the treatment period and for at least 120 days after the last dose of MO-03 and refrain from donating sperm during this period.
• Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix B), not breastfeeding, and at least one of the following conditions applies:

i. Not a woman of childbearing potential (WOCBP) as defined in Appendix B OR ii. Females of child-bearing potential must be willing to use effective contraception during study and for 120 days after the last dose of MO-03.

• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion criteria

• Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration.
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated.

Note: No testing for Hepatitis B is required unless mandated by local health authority.

• Participant must not have uncontrolled diabetes or hypertension in the opinion of treating investigator.
• Participant must not have had a major surgery within 14 days prior to screening.
• Participant must not have severe infection within 14 days prior to enrollment.
• Prohibited Treatments and/or Therapies:

• Any prior chemotherapy, biological therapy, immunotherapy for the current breast cancer diagnosis prior to start of study intervention
• Prior use of immune checkpoint inhibitor is prohibited
• Prior breast surgery or radiation therapy for current invasive breast cancer
• Participants must not have a diagnosis of immunodeficiency and be receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to enrollment.
• Participants must not have active autoimmune disease that has required systemic treatment in 2 years prior to enrollment (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroidreplacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Participants must not have a history of (non-infectious) pneumonitis that required steroids or has current (non-infectious) pneumonitis.
• Any live vaccine within 30 days prior to the first dose of study drug and for 3 months after chemo-immunotherapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Participants on any dose of warfarin. Use of low molecular weight heparin, antithrombin agents, anti-platelet agents or factor Xa inhibitors is allowed
• Participants may not use any other live biotherapeutic products (LBP) or supplementary use of probiotics in pill form during their participation in the study (e.g., Ferring's Rebyota, Vowst)
• Participants may not be currently participating in or participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• Known allergy to any of the components within the study agents and/or their excipients (i.e., corn starch, lactose, microcrystalline cellulose, croscarmellose sodium or magnesium stearate).
• Medical history and concurrent diseases:

• Any prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least five years
• Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (Note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Known history of active TB (Mycobacterium tuberculosis)
• Intercurrent or historic medical condition that increases subject risk in the opinion of the Investigator. Eligibility may be revisited for intercurrent medical conditions once resolution/recovery is deemed adequate by the investigator (e.g., recovery from major surgery, completion of treatment for severe infection).
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has had an allogenic tissue/solid organ transplant.