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

NCT06067061 | Terminated Phase 1 DMC

• 2 other identifiers: IC 2021-102022-502311-12-00
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Triple Negative Breast Neoplasms

Keywords

Triple Negative Breast Cancer; Early-stage; Immunotherapy; Oncolytic virus

Outcome Measures

Primary Outcomes (3)

• Safety of the combination Atezolizumab plus RP1 oncolytic during the safety run-in phase

  Incidence of combination Atezolizumab plus RP1 adverse events (AEs) graded according to NCI CTCAE v5.0 and nature and severity

  9 months

• Toxicity of the combination Atezolizumab plus RP1 oncolytic immunotherapy during the safety run-in phase.

  Dose Limiting Toxicity (DLT) during the first cycle of treatment of the combination Atezolizumab plus RP1 oncolytic immunotherapy

  9 months

• Residual Cancer Burden (RCB) 0-1 during the phase II part

  Rate of RCB 0-1 at time of surgery (in patients with no increase in ctDNA after cycle 3)

  30 months

Secondary Outcomes (9)

• Response rate of RCB Score <= 1 at three cycles

  26 months

• Safety and toxicity of the combination Atezolizumab plus RP1 oncolytic immunotherapy

  60 months

• Invasive disease-free survival (iDFS)

  60 months

• Percentage of TILs

  30 months

• Pre-treatment expression of Programmed Death-Ligand 1 (PD-L1)

  30 months

Study Arms (1)

Atezolizumab plus RP1 (Immulytic™) oncolytic immunotherapy

EXPERIMENTAL

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

Combination Product: Atezolizumab + RP1

Interventions

Atezolizumab + RP1 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.

Also known as: Tecentriq®, Vusolimogene Oderparepvec

Atezolizumab plus RP1 (Immulytic™) oncolytic immunotherapy

Eligibility Criteria

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

You may qualify if:

• Female subject
• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1.
• 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.
• 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.
• Unicentric, unifocal and unilateral disease.
• Tumor-infiltrating lymphocytes (TILs) ≥ 30%, as defined by the International TILs Working Group 2014.
• ctDNA dosing at baseline.
• Agreement to provide tissue samples (tumor biopsy at screening and on-treatment), and at surgery for immune monitoring and translational research activities.
• Agreement to perform blood samples at screening, on-treatment, and at surgery for immune monitoring and translational research activities.

You may not qualify if:

• Inflammatory breast cancer.
• Prior treatment with an oncolytic virus-based therapy.
• Patients with active significant herpetic infections or prior complications of Herpes Simplex Virus-1 (HSV-1) infection.
• Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (e.g., acyclovir).
• Diagnosis of immunodeficiency.
• 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).
• Prior systemic immunosuppressive medication (except physiologic corticosteroid replacement therapy) within 30 days of planned start of study therapy.
• Any live (attenuated) vaccine within 14 days of planned start of study therapy.
• 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.
• Known history of, or any evidence of active, non-infectious pneumonitis.

Sponsors & Collaborators

• Institut Curie: lead
• Replimune Inc.: collaborator
• Roche Pharma AG: collaborator

Study Sites (1)

Institut Curie

Paris, 75005, France

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

atezolizumab; MAPRE1 protein, human

Condition Hierarchy (Ancestors)

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

Study Officials

• Steven Le Gouill, PhD

  Institut Curie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: An open-label, monocentric, single arm, phase II study with a safety run-in.

Study Record Dates

• First Submitted: September 25, 2023
• First Posted: October 4, 2023
• Study Start: April 5, 2024
• Primary Completion: May 7, 2025
• Study Completion: May 7, 2025
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: 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).

Locations

FR (1)