Status and phase
Conditions
Treatments
About
The purpose of this study is to find out if pelareorep in combination with different therapies helps to reduce the growth of breast cancer cells and increase the immune system's response to cancer. This study will also help to understand what this treatment does to the tumor. In addition, the safety of the combination treatments with pelareorep will be evaluated.
Full description
This is a window of opportunity non-randomized exploratory study to evaluate the safety and anti-tumor immunogenicity of pelareorep -/+ atezolizumab in five different cohorts in women with operable early breast cancer.
After enrollment, pelareorep will be administered at 4.5 × 1010 TCID50 intravenously on days 1, 2, 8 & 9. Other therapies will be administered according to the assigned treatment cohort.
After an initial biopsy (diagnostic biopsy in most cases), a second biopsy will be performed on Day 3. Patients will continue the planned treatment until day 21(±5), when a third biopsy will be performed. This third biopsy can be the surgical specimen if patient was scheduled for primary surgery, or a core biopsy if patient will undergo neoadjuvant treatment.
Blood samples will be collected throughout the study at three time points, Day 1, Day 3, and End of Treatment.
Patients will receive treatment for 3 weeks prior to surgery or neoadjuvant therapy. Thereafter, patients will either be considered for definitive surgery or primary medical treatment (e.g. neoadjuvant chemotherapy) at the discretion of the treating physician. Surgery or biopsy prior to neoadjuvant chemotherapy should be done within 3 weeks (±5 days) from the start of the study treatment.
The end of study visit will be performed at the day of surgery. A safety follow-up, the end of study visit, will be done at 28 days (± 7 days) after the last dose of treatment received
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Patient Inclusion Criteria:
Signed written informed consent for all study procedures according to local regulatory requirements prior to beginning specific protocol procedures and assessments.
Female patients.
Age ≥18 years. In cohorts 1 and 2 (patients with HR+/HER2 negative breast cancer), only postmenopausal* patient can be included.
Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast, with all of the following characteristics:
Patient must have biopsiable disease.
Histologically confirmed HER2 status and hormone receptors (ER and PgR) according to ASCO/CAP guidelines locally assessed.
ECOG Performance Status of 0 or 1.
Adequate organ function, as determined by the following laboratory tests, within 14 days prior to randomization:
Hematological
Renal
o Serum creatinine ≤ 1.5 x upper limit of normal (ULN), or 24-hour creatinine clearance ≥ 60 mL/min for subject with creatinine levels > 1.5 x ULN. (Note: Creatinine clearance does not need to be determined if the baseline serum creatinine is within normal limits. Creatinine clearance should be calculated per institutional standard).
Hepatic
Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (only for cohorts 3 to 5 and pre-menopausal women or non-confirmed postmenopausal* status).
Patient Exclusion Criteria
Inoperable locally advanced or inflammatory (i.e., inoperable Stage III) breast cancer.
Metastatic (Stage IV) breast cancer.
Bilateral invasive breast cancer.
Multicentric breast cancer, defined as the presence of two or more foci of cancer in different quadrants of the same breast.
Prior therapy for breast cancer.
Prior therapy with an anti- PD-1, anti- PD-L1, anti-PD-L2, anti-CD137 antibody, or anti-CTLA-4 antibody compound, Pelareorep or any other oncolytic viruses.
Prior therapy with tumor vaccine
History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy or evidence of clinically significant immunosuppression. Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Treated or untreated hyperthyroidism. Uncontrolled hypothyroidism (patients with controlled and asymptomatic hypothyroidism can be included)
Received any vaccine, including against SARS-COV-2 (COVID-19), <14 days prior to the first day of study treatment. Inactivated vaccines (including against COVID-19 or seasonal influenza) are permitted after surgery.
History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome.
Evidence of clinically significant immunosuppression such as the following:
Cardiopulmonary dysfunction as defined by:
Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary or metabolic disease; wound healing disorders; ulcers; bone fractures).
Major surgical procedure or significant traumatic injury within approximately 28 days prior to enrollment or anticipation of the need for major surgery during the course of study treatment.
Concurrent, serious, uncontrolled infections or current known infection with HIV or active hepatitis B and/or hepatitis C.
Assessment by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
Known history of active Bacillus tuberculosis.
History of significant co-morbidities that, in the judgment of the Investigator, may interfere with the conduction of the study, the evaluation of response, or with informed consent.
Primary purpose
Allocation
Interventional model
Masking
26 participants in 6 patient groups
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Data sourced from clinicaltrials.gov
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