IIT2021-01-Shiao-CSF1Ri: Reinvigorating TNBC Response to Immunotherapy With Combination Myeloid Inhibition and Radiation
This is an open-label prospective, single institution, Phase II study of pembrolizumab in combination with radiation therapy and CSF-1R inhibition in patients with high-risk TNBC. The primary objective is to assess the pathologic complete response (pCR) rate where pCR is defined as the absence of invasive disease in the breast and lymph nodes at the time of standard of care (SOC) treatment. Secondary objectives include evaluating the change in tumor infiltrating lymphocytes (TILs), safety and tolerability of the combination, progression-free survival, event-free survival, overall survival, and node clearance.
• Female patients diagnosed with high-risk triple negative breast cancer (TNBC) with intent for neoadjuvant therapy.
• Low tumor-infiltrating lymphocyte (TIL) score, defined as stromal TIL (sTIL) ≤40%; or node-positive; or combined positive score (CPS) \< 10 or PD-L1 tumor positivity \<1%.
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study, including consent for research blood draws and use of available archived tissue.
• Age ≥ 18 years of age on day of signing informed consent.
• Histologically or cytologically-confirmed TNBC (defined as ER \<1%, PR\<1%, her-2-neu 0-1+ by IHC or FISH-negative).
• If an archived tumor tissue is unavailable, be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1 of RT.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function.
• Female subject of childbearing potential should have a negative serum or urine pregnancy test or documentation of absence of pregnancy by a gynecologist within 14 days of initiating first dose of pembrolizumab (1 week lead-in) for eligibility verification.
• Female subjects of childbearing potential should be willing to comply to the contraceptive guidance in Appendix 12.2 during the treatment period through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.