CMP-001 and Pre-operative Stereotactic Body Radiation Therapy (SBRT) in Early Stage Triple Negative Breast Cancer (TNBC)

NCT04807192 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: CHUV-DO-0009-CyberImmunoBreast
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, randomized, window-of-opportunity phase 2 clinical study evaluating the biological activity of preoperative Stereotactic Body RadioTherapy (SBRT) alone (Arm 1), and combined with subcutaneous (SC) followed by intra-tumoral (IT) administrations of CMP-001 (Arm 2), in subjects with early stage TNBC. Safety and efficacy of the treatments are also examined. The main hypothesis that the study treatment induces an increase in stromal tumor infiltrating lymphocytes (sTILs) will be explored in each arm separately. The study is designed as a randomized selection study, with randomization used to address patient selection bias while each arm is run as an independent study. No formal statistical comparison between the two arms is planned. 40 patients will be equally (1:1) randomized in this study (20 per arm), stratified into two groups according to primary treatment strategy (upfront surgery versus neoadjuvant chemotherapy).

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• To assess and describe independently in each arm the biological activity (increase in sTILs) of CMP-001 combined with SBRT and of SBRT alone in patients with early stage TNBC in a preoperative setting

  A 10% increase in the presence of TILs (between baseline and surgery/biopsy before start of the neoadjuvant chemotherapy) is the defined threshold for efficacy. Percentage of sTILs will be quantified using hematoxylin and eosin (H\&E) staining and immunohistochemistry (IHC) as per current consensus.

  Evaluated between baseline and surgery (up to 7 weeks)

Secondary Outcomes (11)

• Toxicity of CMP-001 combined with SBRT and of SBRT alone

  (S)AEs collected continuously from the time of informed consent signature until end of treatment visit, which correspond to Day 51 to 60.

• Tumor response: pCR and pPR

  evaluation at surgery (between day 21 and day 30 post-SBRT) or change from baseline to surgery (up to 7 weeks)

• Tumor response: residual tumor cells

  evaluation at breast biopsy (between day 16 and day 30 post-SBRT)

• Tumor response: minimal residual cancer

  evaluation at surgery (between day 21 and day 30 post-SBRT) or change from baseline to surgery (up to 7 weeks)

• Tumor response: Ki-67

  evaluation at surgery (between day 21 and day 30 post-SBRT) or change from baseline to surgery (up to 7 weeks)

Study Arms (2)

Arm 1: SBRT

EXPERIMENTAL

Radiation: stereotactic body radiotherapy

Arm 2: CMP-001 + SBRT

EXPERIMENTAL

Radiation: stereotactic body radiotherapy; Drug: CMP-001

Interventions

stereotactic body radiotherapy RADIATION

one administration of SBRT 8 Gy at D1

Arm 1: SBRT; Arm 2: CMP-001 + SBRT

CMP-001 DRUG

4 sequential administrations of CMP001 at Day 1 (SC), Day 5 (±1) (IT), Day 9 (±1) (IT) and Day 16 (±1) (IT)

Arm 2: CMP-001 + SBRT

Eligibility Criteria

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

You may qualify if:

• Signed study Informed Consent Form prior to the initiation of any study procedures
• Women age ≥18 years
• Histologically confirmed diagnosis of triple negative breast cancer (TNBC) of early stage (cT1b-2, cN0-3b cM0) determined according to immunohistochemistry (IHC) / in situ hybridization (ISH). TNBC subtype is defined as:
• Estrogen receptor (ER) \<10%
• Progesterone receptor (PR) \<10%
• Human epidermal growth factor receptor 2 (HER2) negative (not eligible for anti-HER2 therapy) defined as:
• IHC 0, 1+ without ISH or
• IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 6 signals/cells or
• ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 6 signals/cells (without IHC)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Women with bilateral breast TNBC can be acceptable if both sides are TNBC (treatment is allowed to be administered to one breast only).
• Capable of understanding and complying with protocol requirements
• A planned breast surgery (Breast conserving surgery \[BCS\] or mastectomy) or neoadjuvant chemotherapy.
• Presence of measurable disease in the breast, defined as a lesion that can be accurately measured in at least one dimension with conventional techniques (Magnetic resonance imaging \[MRI\] and/or ultrasound)
• Primary tumor accessible to injections and biopsy. Multifocal and multicentric disease is allowed and the most accessible lesion will be injected. The lesion to be injected should be confined in a single irradiation volume that does not result in more than 30% of the whole breast.

You may not qualify if:

• Subjects presenting with any of the following do not qualify for entry into the study:
• Breast-feeding women
• Medical history and concurrent diseases:
• History of malignancy other than TNBC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \>90%), such as adequately treated carcinoma of the cervix in situ, non-melanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer
• Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Developed autoimmune disorders of Grade 4 while on prior immunotherapy. Subjects who developed autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤ 1 and the subject has been off systemic steroids for at least 2 weeks.
• Any concurrent uncontrolled illness, including mental illness or substance abuse, which in the opinion of the Investigator, would make the subject unable to cooperate and participate in the trial
• Severe uncontrolled cardiac disease within 6 months before Screening, including but not limited to uncontrolled hypertension; unstable angina; myocardial infarction (MI) or cerebrovascular accident (CVA)
• Active autoimmune disease:
• Participants with well controlled asthma and/or mild allergic rhinitis (seasonal allergies) are eligible
• Participants with the following disease conditions are also eligible:
• Vitiligo
• Type 1 diabetes mellitus
• Residual hypothyroidism due to autoimmune condition only requiring hormone replacement
• Psoriasis not requiring systemic treatment conditions not expected to recur in the absence of an external trigger are permitted to enroll

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

CHUV Oncology Department

Lausanne, Canton of Vaud, 1011, Switzerland

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Medical director of the Breast Center at CHUV

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: March 19, 2021
• Study Start: April 7, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)