A Window-of-opportunity Study of Pelareorep in Early Breast Cancer

NCT04102618 | Terminated Early Phase 1 DMC

• 1 other identifier: REO 027
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast; Breast Cancer; Primary Breast; Primary Breast Cancer; Pelareorep; Atezolizumab; Reovirus; Oncolytic virus; Letrozole; Early Breast Cancer; Triple-negative breast cancer; HR+ breast cancer; HER2+ breast cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate if pelareorep in combination with different therapies increases the value of the CelTIL score in women with operable early breast cancer. CelTIL is a combined IHC-based score based on tumor cellularity and stromal TILs.

  CelTIL score is a metric for quantifying broad changes to the tumor microenvironment and is calculated by the following equation: CelTIL score = -0.8 × tumor cellularity (in percent) + 1.3 × TILs (in percent). The minimum and maximum unscaled CelTIL scores will be -80 and 130. This unscaled CelTIL score will then be scaled to reflect the reported values ranging from 0 to 100 points where an increase in CelTIL scores represent favorable changes to the tumor microenvironment.

  The CelTIL score will be measured from on-treatment tumor biopsies collected at baseline (pre-treatment), day 3, and at time of surgery (day ~21 ± 5 days).

Secondary Outcomes (4)

• To evaluate if pelareorep in combination with different therapies increases the value of the CelTIL score in women with HR+/HER2-negative breast cancer.

  The CelTIL score will be measured from on-treatment tumor biopsies collected at baseline (pre-treatment), day 3, and at time of surgery (day ~21 ± 5 days).

• To evaluate if pelareorep in combination with different therapies increases the value of the CelTIL score in women with HER2-positive breast cancer.

  The CelTIL score will be measured from on-treatment tumor biopsies collected at baseline (pre-treatment), day 3, and at time of surgery (day ~21 ± 5 days).

• To identify biological changes, as defined by gene expression between posttreatment and pretreatment samples following pelareorep in combination with different therapies.

  throughout

• To describe the safety profile of the combination therapies

  throughout

Study Arms (6)

Cohort 1 (closed to enrollment)

EXPERIMENTAL

HR+/HER2-neg patients who will receive pelareorep plus letrozole

Biological: Pelareorep; Drug: Letrozole

Cohort 2 (closed to enrollment)

EXPERIMENTAL

HR+/HER2-neg patients who will receive pelareorep plus letrozole plus atezolizumab

Biological: Pelareorep; Drug: Letrozole; Drug: Atezolizumab

Cohort 3 (closed to enrollment)

EXPERIMENTAL

TNBC patients who will receive pelareorep plus atezolizumab

Biological: Pelareorep; Drug: Atezolizumab

Cohort 4 (closed to enrollment)

EXPERIMENTAL

HER2+/HR+ patients who will receive pelareorep plus trastuzumab plus atezolizumab

Biological: Pelareorep; Drug: Atezolizumab; Drug: Trastuzumab

Cohort 5 (closed to enrollment)

EXPERIMENTAL

HER2+/HR- patients who will receive pelareorep plus trastuzumab plus atezolizumab

Biological: Pelareorep; Drug: Atezolizumab; Drug: Trastuzumab

Cohort 6

EXPERIMENTAL

HER2+ (irrespective of HR status) (6 patients) who will receive pelareorep + trastuzumab

Biological: Pelareorep; Drug: Trastuzumab

Interventions

Pelareorep BIOLOGICAL

4.5 × 10e10 TCID50 administered intravenously on Days 1, 2, 8 \& 9

Also known as: Previously REOLYSIN®

Cohort 1 (closed to enrollment); Cohort 2 (closed to enrollment); Cohort 3 (closed to enrollment); Cohort 4 (closed to enrollment); Cohort 5 (closed to enrollment); Cohort 6

Letrozole DRUG

Oral dose of 2.5 mg/day starting on Day 3 for 13 days

Cohort 1 (closed to enrollment); Cohort 2 (closed to enrollment)

Atezolizumab DRUG

1200 mg administered intravenously on Day 3

Cohort 2 (closed to enrollment); Cohort 3 (closed to enrollment); Cohort 4 (closed to enrollment); Cohort 5 (closed to enrollment)

Trastuzumab DRUG

8mg/kg administered intravenously or 600mg subcutaneously on Day 3

Cohort 4 (closed to enrollment); Cohort 5 (closed to enrollment); Cohort 6

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• At least 1 lesion that can be measured in at least 1 dimension with ≥ 10 mm in largest diameter measured by ultrasound and mammogram.
• Documentation confirming the absence of distant metastasis (M0) as determined by institutional practice. Routine exams to discard metastases will be performed according to Investigator judgement but are mandatory in case of suspicion of metastatic disease.
• Breast cancer eligible for primary surgery.
• In the case of a multifocal tumor (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be ≥ 10 mm and designated the "target" lesion for all subsequent tumor evaluations and biopsies.
• Patient must have biopsiable disease.
• Histologically confirmed HER2 status and hormone receptors (ER and PgR) according to ASCO/CAP guidelines locally assessed.
• Invasive TNBC defined as: ER and PR negative defined as IHC nuclear staining \<1% AND HER2 negative.
• HR+/HER2 negative defined as: ER and PR positive defined as IHC nuclear staining \>1% AND HER 2 negatives.
• HER2 positive defined as; IHC +++ or FISH positive.
• ECOG Performance Status of 0 or 1.
• Adequate organ function, as determined by the following laboratory tests, within 14 days prior to randomization:

You may not qualify if:

• 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:
• diagnosis of immunodeficiency
• concurrent opportunistic infection
• receiving systemic immunosuppressive therapy (\> 2 weeks) or within 7 days prior to the first dose of study treatment, including oral steroid doses \> 10 mg/day of prednisone or equivalent. Subjects that require intermittent use of bronchodilators or local steroid injection will not be excluded from the study.

Sponsors & Collaborators

• Oncolytics Biotech: lead
• SOLTI Breast Cancer Research Group: collaborator

Study Sites (14)

ICO Badalona

Badalona, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital Quirón Dexeus

Barcelona, Spain

Location

Hospital Moisés Broggi

Esplugues de Llobregat, Spain

Location

Hospital Fuenlabrada

Madrid, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital Puerta de Hierro de Majadahonda

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain

Location

Hospital Clínico Universitario Virgen Arrixaca

Murcia, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Instituto Valenciano de Oncología

Valencia, Spain

Location

Hospital Clínico Lozano Blesa

Zaragoza, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

reolysin; Letrozole; atezolizumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2019
• First Posted: September 25, 2019
• Study Start: March 29, 2019
• Primary Completion: April 20, 2022
• Study Completion: April 20, 2022
• Last Updated: August 15, 2022

Record last verified: 2022-08

Locations

ES (14)