"neoBREASTIM": Atezolizumab Plus RP1 Oncolytic Immunotherapy in the NeoAdjuvant Setting of Triple-Negative Breast Cancer

NCT ID: NCT06067061

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-05
• Study Completion Date: 2025-05-07

Brief Summary

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.

Detailed Description

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.

Conditions

Triple Negative Breast Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezolizumab plus RP1 (Immulytic™) oncolytic immunotherapy

Atezolizumab IV q2w RP1 (Immulytic™) by imaging-guided intra-tumor (IT) route.

Group Type: EXPERIMENTAL

Atezolizumab + RP1

Intervention Type: COMBINATION_PRODUCT

Patients will be treated in a window period (ie 3 treatment cycles). After evaluation, patients that had no increase in ctDNA after 3 cycles (see Definition of ctDNA status) will continue on the same treatment (intratumoral injections of RP1 in combination with Atezolizumab) for a total of 10 treatment cycles prior to surgery.

Interventions

Atezolizumab + RP1

Patients will be treated in a window period (ie 3 treatment cycles). After evaluation, patients that had no increase in ctDNA after 3 cycles (see Definition of ctDNA status) will continue on the same treatment (intratumoral injections of RP1 in combination with Atezolizumab) for a total of 10 treatment cycles prior to surgery.

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Tecentriq®; Vusolimogene Oderparepvec

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Replimune Inc.

INDUSTRY

Sponsor Role: collaborator

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Institut Curie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Le Gouill, PhD

Role: STUDY_DIRECTOR

Institut Curie

Locations

Institut Curie

Paris, , France

Countries

France

Other Identifiers

2022-502311-12-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

IC 2021-10

Identifier Type: -

Identifier Source: org_study_id