This phase II trial studies how well chemokine modulation therapy works when given prior to pembrolizumab in treating patients with triple-negative breast cancer that has spread to other places in the body (metastatic). Drugs used in chemokine modulation therapy, such as celecoxib, recombinant interferon alfa-2b, and rintatolimod, work by unleashing or enhancing the cancer immune responses that already exist by either blocking inhibitory molecules or by activating stimulatory molecules. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving chemokine modulation therapy before pembrolizumab may work better in treating patients with metastatic triple-negative breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03599453.
PRIMARY OBJECTIVE:
I. To evaluate the increase of CD8+ infiltration into tumor microenvironment after pre-treatment chemokine modulation (CKM) regimen.
SECONDARY OBJECTIVES:
I. To evaluate the overall response rate (ORR) to the combination therapy per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
II. To evaluate the efficacy of the CKM in combination with pembrolizumab in patients with metastatic triple negative breast cancer (mTNBC) as compared to historic outcomes of pembrolizumab and other anti-PD1/PD-L1 therapies alone, as determined by secondary measures of efficacy including: progression-free survival (PFS), overall survival (OS), disease control rate (DCR).
III. To evaluate the safety profile of CKM regimen given as pre-treatment to pembrolizumab therapy in metastatic breast cancer patients using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
EXPLORATORY OBJECTIVES:
I. Examine the immune analysis profile of CKM and pembrolizumab combination.
II. Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and genetic markers, and their associated PD-1, CD45RA or CD45RO levels.
III. Correlate PD-L1 expression within both neoplastic and nonneoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and adverse events (AEs).
IV. Correlate Immune Panel results with ORR, PFS, OS and AEs.
V. Comparison of response assessment criteria for a prospective analysis.
OUTLINE:
Patients undergo pre-treatment biopsy. Patients then undergo chemokine modulation therapy consisting of celecoxib orally (PO) twice daily (BID), recombinant interferon alfa-2b intravenously (IV) over 20 minutes, and rintatolimod IV over 30-60 minutes on days -11 to -9, and -4 to -2. Patients then undergo additional biopsy. Following biopsy and chemokine modulation therapy, patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days and then every 6 months for up to 2 years.
Lead OrganizationRoswell Park Cancer Institute
Principal InvestigatorShipra Gandhi
