insufficient recruitment

Neoadjuvant treatment is an important part of the treatment strategy for locally advanced TNBC having established a positive and significant correlation of pathologic Complete Response (pCR) with long-term clinical benefit such as Event-Free Survival (EFS) and Overall Survival (OS) as shown via large meta-analysis. Much effort has been made to identify novel agents and new drug combinations that can improve pCR rates in this specific clinical setting, which is the leading rationale to evaluate RP1 oncolytic immunotherapy in combination with Atezolizumab.

The combination of RP1 plus Atezolizumab, while being expected to result in increased efficacy, is not expected to result in significant additional toxicity, as compared to either agent alone. Capitalizing on the strong prognostic and predictive value of the TIL infiltrate in early-stage TNBC and the capacity of circulating tumor DeoxyriboNucleic Acid (ctDNA) detection to predict response to immunotherapy and NeoAdjuvant Chemotherapy (NAC), neoBREASTIM - a single-arm phase 2 study - will evaluate a novel, biomarker-driven combination of Atezolizumab plus RP1 oncolytic immunotherapy in the neo-adjuvant setting of patients diagnosed with early-stage, TIL-high TNBC.

Inclusion Criteria:

1. Female subject
2. Age ≥ 18 years old.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1.
4. Newly diagnosed Triple-Negative Breast Cancer (TNBC), defined as the absence of estrogen expression and progesterone expression, and of Human Epidermal growth factor Receptor 2 (HER2) overexpression, must be determined by local testing of a screening tumor sample as defined by American Society of Clinical Oncology/College of American Pathologists guidelines.
5. TNBC defined as the following combined primary tumor (T), regional lymph node (N), and metastatic (M) American Joint Committee on Cancer staging criteria: cT ≥15 - ≤30 mm, N0, M0 according to Mammogram, breast Ultrasound and MRI, and PET-CT. In case of a difference in the measurement of the primary tumor among different imaging methods, the breast MRI measurement is the reference.
6. Unicentric, unifocal and unilateral disease.
7. Tumor-infiltrating lymphocytes (TILs) ≥ 30%, as defined by the International TILs Working Group 2014.
8. ctDNA dosing at baseline.
9. Agreement to provide tissue samples (tumor biopsy at screening and on-treatment), and at surgery for immune monitoring and translational research activities.
10. Agreement to perform blood samples at screening, on-treatment, and at surgery for immune monitoring and translational research activities.

Exclusion Criteria:

1. Inflammatory breast cancer.
2. Prior treatment with an oncolytic virus-based therapy.
3. Patients with active significant herpetic infections or prior complications of Herpes Simplex Virus-1 (HSV-1) infection.
4. Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (e.g., acyclovir).
5. Diagnosis of immunodeficiency.
6. Has active autoimmune disease (e.g. inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, and multiple sclerosis, celiac disease, Wegener's granulomatosis) that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
7. Prior systemic immunosuppressive medication (except physiologic corticosteroid replacement therapy) within 30 days of planned start of study therapy.
8. Any live (attenuated) vaccine within 14 days of planned start of study therapy.
9. Prior immunotherapy, including tumor vaccine, cytokine, anti-CTLA4, PD-1/PD-L1 blockade or similar agents, T cell receptor-based (TCR-based) or Chimeric Antigen Receptor-T (CAR-T) cell based adoptive cell therapy.
10. Known history of, or any evidence of active, non-infectious pneumonitis.

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.

Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).