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

Triple Negative Breast Cancer Clinical Trial

Official title: CMP-001 in Combination With Pre-Operative Stereotactic Body Radiation Therapy in Patients With Early Stage Triple Negative Breast Cancer: An Open-Label, Window of Opportunity, Randomized Phase 2 Clinical Study

Status Recruiting

Clinical Trial Summary

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).

Clinical Trial Description

This is a Phase 2, proof of principle study that explores the therapeutic window between diagnosis and surgery in patients with early stage invasive TNBC not being candidates for neo-adjuvant chemotherapy.

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 SBRT with or without CpG (CMP-001), a toll-like receptor (TLR) 9 agonist will induce an increase in sTILs in the tumor in patients with early invasive TNBC, which theoretically should improve those patients' prognosis.

There is growing evidence indicating that radiotherapy (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 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 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. ;

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

• NCT number: NCT04807192
• Study type: Interventional
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: Lana Kandalaft, Pharm D, PhD
• Phone: +41213147823
• Email: do.ion.ref@chuv.ch
• Status: Recruiting
• Phase: Phase 2
• Start date: April 8, 2021
• Completion date: December 2025