CMP-001 and Pre-operative Stereotactic Body Radiation Therapy (SBRT) in Early Stage Triple Negative Breast Cancer (TNBC)

This is an open-label, randomized, window-of-opportunity phase 2 clinical study evaluating the biological activity of preoperative Stereotactic Body RadioTherapy (SBRT) alone (Arm 1), and combined with subcutaneous (SC) followed by intra-tumoral (IT) administrations of CMP-001 (Arm 2), in subjects with early stage TNBC. Safety and efficacy of the treatments are also examined.

The main hypothesis that the study treatment induces an increase in stromal tumor infiltrating lymphocytes (sTILs) will be explored in each arm separately.

The study is designed as a randomized selection study, with randomization used to address patient selection bias while each arm is run as an independent study. No formal statistical comparison between the two arms is planned.

40 patients will be equally (1:1) randomized in this study (20 per arm), stratified into two groups according to primary treatment strategy (upfront surgery versus neoadjuvant chemotherapy).

This is a Phase 2, proof of principle study that explores the therapeutic window between diagnosis and upfront surgery or start of the neoadjuvant chemotherapy in patients with early stage invasive TNBC.

The presence of tumor infiltrating lymphocytes (TILs) within the tumors of patients with early invasive TNBC has been associated with improved prognosis. The hypothesis of this study is that pre-operative stereotactic radiotherapy (SBRT) and SBRT combined with CpG (CMP-001), a Toll-like receptor (TLR) 9 agonist will induce an increase in stromal TILs (sTILs) in the tumor in patients with early invasive TNBC, which theoretically should improve those patients' prognosis.

There is growing evidence indicating that RT induces massive release of tumor-associated antigens (TAAs) during cancer cell death. RT enhances tumor immunogenicity and increases the presence of effector immune cells to the tumor site. It increases availability of tumor antigens and promotes antigen capture, cell migration to the lymph nodes, polarization towards a tolerogenic or immunogenic phenotype or migration of lymphocytes into the tumor. Doses of around 8 Gray (Gy) induce more important immune infiltration.

SBRT is a precise technique of irradiation within the tumor permitting high dose delivery in a safe manner with tight margins. In our study, the irradiated tissue will then be removed by surgery, allowing for standard of care irradiation to be administered postoperatively. However, the preoperative SBRT on the tumor might increase intratumoral or stromal TILs' presence.

CMP-001 (vidutolimod, CYT003, QbG10) has already been shown to increase CD8+ T cell intratumoral infiltration in early clinical data, and ongoing data of a phase Ib clinical trial combining intratumoral (IT) injections of CMP-001 (3-10 mg) in melanoma lesions with Pembrolizumab show rapid abscopal responses in other skin lesions after 3 injections. The combination of IT CMP-001 and SBRT, through increased TAA release and immunologic enhancement due to the TLR9 agonist, might ultimately result in a clinically meaningful " in-situ vaccination " effect through enhancement of the host's antitumor immunity, promoting immune eradication of micrometastatic disease. The TNBC population is prone to micrometastatic disease, even at early stages; therefore any of these experimental treatments might result in increased TILs' infiltration, which theoretically would bring potential benefits in distant control of the disease and overall survival improvements.

Eligibility

Relevant conditions:

Triple Negative Breast Cancer

If you aren't sure if you meet the criteria above speak to your healthcare professional. Criteria may be updated but not reflected here, do not hesitate to contact the trial if you think are close to fitting criteria.

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Data sourced from ClinicalTrials.gov