Combination Immunotherapy Treatment for Locally Advanced Unresectable or Metastatic, PD-L1 Negative (CPS<10), gBRCA Negative, Triple Negative Breast Cancer Including BreakVax ImmunoTreatment (Designed and Manufactured Per Patient), Chemotherapy and Anti PD-1 Therapy

NCT07762703 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: BreakBio-3 Substudy A
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the safety, feasibility, and preliminary antitumor activity of this multi-component immunotherapy strategy in patients with advanced solid tumors. The study is designed to assess whether coordinated enhancement of antigen-specific T-cell priming and tumor microenvironment modulation can improve immune-mediated tumor control. In this study, BreakVax with adjuvants (Montanide and Poly-ICLC) is administered in combination with:

1. 1.Low-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming;
2. 2.Pembrolizumab to mitigate PD-1-mediated T-cell exhaustion and sustain effector function;
3. 3.Standard-of-care chemotherapy, which may promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment; and
4. 4.Losartan and aspirin, which have been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling.

Conditions

Triple-Negative Breast Cancer (TNBC)

Keywords

Triple Negative Breast Cancer; PD-L1 negative; gBRCA negative; Locally Advanced; Unresectable; Metastatic

Outcome Measures

Primary Outcomes (4)

• Immune-related Objective Response Rate (irORR) per iRECIST Assessed by Independent Review Committee

  Percentage of treated participants who achieve a confirmed immune complete response (iCR) or immune partial response (iPR) according to iRECIST, as assessed by a central independent review committee (IRC). For participants randomized to the Delayed BreakVax Arm, only responses occurring before initiation of BreakVax following progression on chemotherapy will be included in the primary irORR analysis.

  From start of assigned treatment through disease progression; for the Delayed BreakVax Arm, through progression on chemotherapy before crossover to BreakVax, up to 2 years

• Disease Control Rate (DCR) Following Crossover to BreakVax Combination Treatment

  Percentage of participants in the Delayed BreakVax Arm who experience disease progression while receiving standard-of-care chemotherapy and subsequently achieve disease control after crossover to the BreakVax combination treatment. Disease control is defined as complete response, partial response, or stable disease according to iRECIST.

  From initiation of BreakVax combination treatment after crossover through subsequent disease progression, up to 2 years

• Percentage of patients for whom BreakVax is successfully manufactured

  Percentage of enrolled participants for whom a patient-specific BreakVax drug product is successfully manufactured and available for administration according to protocol-defined manufacturing requirements.

  up to 24 Months

• Adverse events

  Number and percentage of participants experiencing treatment-emergent adverse events

  up to 24 Months

Secondary Outcomes (9)

• Change in Tumor T-cell Infiltration Between Pre-treatment and On-treatment Biopsies

  Baseline to approximately Cycle 3 after imaging

• Progression-Free Survival (PFS) per RECIST v1.1

  From start of study treatment to disease progression or death, up to 2 years

• Duration of Response (DoR) per RECIST v1.1

  From first documented CR or PR to disease progression, up to 2 years

• Clinical Benefit Rate (CBR) per RECIST v1.1

  From start of study treatment through disease progression, up to 2 years

• Objective Response Rate (ORR) per RECIST v1.1

  From start of study treatment through disease progression, up to 2 years

Other Outcomes (3)

• T-cell priming

  24 Months

• Tumor T-cell infiltration

  24 Months

• Tumor microenvironment modulation

  24 Months

Study Arms (2)

BreakVax Arm

EXPERIMENTAL

A treatment cycle is defined as 21 days. BreakVax Arm: BreakVax, in combination with its adjuvants and low-dose subcutaneous ipilimumab (as a local dendritic cell adjuvant) will be administered on Day 1 of Cycles 1, 2, and 3. Thereafter, BreakVax will be administered on Day 1 of every even cycle (i.e. cycles 4, 6, 8, etc.) until disease progression per iRECIST or other discontinuation criteria. In addition to BreakVax: * Losartan will be administered orally once daily throughout treatment. * Chemotherapy of physician's choice will be administered per the selected regimen within each cycle. * Aspirin will be administered orally once daily, except on Days 1, 2, and 3 of cycles in which BreakVax is administered. * Pembrolizumab will be initiated on Day 10 of Cycle 4 and will thereafter be administered on Day 10 of every even-numbered cycle (i.e., Cycles 4, 6, 8, etc.) until disease progression or discontinuation

Drug: BreakVax; Drug: Ipilimumab 2.5 mg; Drug: Pembrolizumab; Drug: Standard-of-care chemotherapy; Drug: Losartan and aspirin

Delayed BreakVax Arm

ACTIVE COMPARATOR

Patients randomized to the Delayed BreakVax Arm will receive chemotherapy of physician's choice in each 21-day cycle until disease progression per iRECIST. Upon documented disease progression, patients will cross over to receive the full combination regimen, including BreakVax with adjuvants, low-dose subcutaneous ipilimumab (as a local dendritic cell adjuvant), pembrolizumab, losartan, aspirin, and chemotherapy of physician's choice, according to the BreakVax Arm schedule

Drug: Standard-of-care chemotherapy

Interventions

BreakVax DRUG

BreakVax (BB-101) is an investigational, personalized peptide-based cancer immunotherapy designed to stimulate patient-specific antitumor T-cell responses. For each patient, tumor tissue undergoes integrated genomic, transcriptomic, and proteomic analysis to identify tumor-associated antigens (TAAs) and tumor-specific neoantigens (TSAs). A proprietary selection algorithm prioritizes peptides predicted to be presented by the patient's HLA molecules and selectively expressed or overexpressed in tumor tissue. The resulting individualized peptide pools are manufactured, formulated with adjuvants (Montanide ISA 51 and Poly-ICLC), and administered subcutaneously

BreakVax Arm

Ipilimumab 2.5 mg DRUG

A local dendritic cell adjuvant injected adjacent to the BreakVax site to promote antigen presentation and T-cell priming

BreakVax Arm

Pembrolizumab DRUG

To mitigate PD-1-mediated T-cell exhaustion and sustain effector function

BreakVax Arm

Standard-of-care chemotherapy DRUG

May promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment

BreakVax Arm; Delayed BreakVax Arm

Losartan and aspirin DRUG

Have been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling

BreakVax Arm

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and \< 72
• Patients with histologically confirmed locally advanced unresectable or metastatic, PD-L1 negative (CPS \<10), gBRCA-negative TNBC who received first-line ADC treatment and experienced disease progression and have sent 200mg (approximately) of tumor tissue (fresh tissue immersed in AllProtect then frozen) to BreakBio for analysis.
• Must have measurable disease per RECIST v1.1 (at least one non-nodal lesion ≥10 mm in longest diameter and/or pathologic lymph node(s) ≥15 mm in short axis on CT/MRI) on imaging obtained within 21 days of first dose of treatment combination.
• Must not have experienced progression during the induction chemotherapy cycles.
• Eastern Cooperative Oncology Group (ECOG) performance status = 0 or 1 on day of first dose
• Patient has adequate organ function on day one of the trial as defined by:
• Neutrophil to Lymphocyte Ratio (NLR)1 at a healthy adult's normal level: ≤ 3.5
• Absolute Neutrophil Count (ANC) at the normal level: ≤ 7,000/mm3
• Absolute Lymphocyte Count in normal level: ≥ 1,000/mm3
• Monocytes at normal level: \< 700/mm3
• Platelet count: ≥ 100 x 109/L (without transfusion support in the last two weeks)
• Hemoglobin: \> 10.0 g/dL (without transfusion support in the last two weeks)
• AST and ALT: ≤ 3 X institutional upper limit of normal (ULN) in the absence of liver mets; AST and/or ALT may be ≤ 5 x ULN in the setting of liver metastases
• Total Bilirubin: ≤ 1.2mg/dL
• Serum creatinine: ≤ 1.5 x institution's ULN

You may not qualify if:

• Prior exposure to anti PD- 1/PD-L1 agents.
• Prior exposure to immunosuppressive therapy within the last 12 months prior to enrollment
• Receiving or previously receiving oral or IV steroids within 6 weeks of starting study treatment. Currently using or previously used topical steroids within 6 weeks of starting study treatment. Expected to require steroid-containing pre-meds before chemotherapy doses.
• Patients with deficient mismatch repair (dMMR) or microsatellite instability (MSI-H) phenotype.
• Any liver metastasis greater than 2 cm or greater than 5 liver metastases. Patients who have liver metastasis removed by surgery, and therefore meet this criterion at first dose, may enroll.
• Patients not recovered from all clinically significant toxic effects of previous therapies to ≤Grade 1 or baseline with the exception of peripheral neuropathy and alopecia.
• Patients not recovered adequately from the toxicity and/or complications from any major surgery prior to starting study treatment.
• Known or suspected hypersensitivity to any of the study drugs
• Received an investigational agent within 28 days prior to the first dose of study drug.
• History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction within the past 6 months. Note: Prior to trial entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• LVEF \<50%
• Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
• Untreated, symptomatic, or progressing brain/CNS metastases; leptomeningeal disease; or prior whole-brain radiation. CNS metastases are allowed only if treated and stable on MRI for ≥8 weeks, the patient has recovered from CNS therapy, and has been off steroids for ≥12 weeks.
• Known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. (Individuals who are hepatitis C antibody positive may be enrolled if negative viral load confirmed).
• History of autoimmune disease including: inflammatory bowel disease (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g. Wegener's granulomatosis); central nervous system or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barré syndrome, myasthenia gravis, multiple sclerosis). Individuals with vitiligo, Sjogren's Syndrome, interstitial cystitis, Graves' or Hashimoto's Disease, celiac disease, DM1, hypothyroidism stable on hormone replacement, or any autoimmune disease without symptoms and not requiring active therapy for at least 2 years will be allowed with Study Medical Monitor's approval.

Sponsors & Collaborators

• BreakBio Corp: lead
• Miami Cancer Institute: collaborator

Study Sites (1)

Miami Herbert Wertheim Cancer Institute

Miami, Florida, 33176, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

Ipilimumab; pembrolizumab; Losartan; Aspirin

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Salicylates; Hydroxybenzoates; Phenols

Study Design

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

Model Details: 10 patients will be randomized in a 1:1 ratio to one of the following arms: * BreakVax Arm: BreakVax formulated with adjuvants and low-dose subcutaneous ipilimumab (as a local dendritic cell adjuvant) in combination with pembrolizumab, losartan, aspirin, and SOC chemotherapy of physician's choice. * Delayed BreakVax Arm: SOC chemotherapy of physician's choice until disease progression per iRECIST. Upon progression, patients will cross over to receive the study combination regimen, including BreakVax formulated with adjuvants, low-dose subcutaneous ipilimumab (as a local dendritic cell adjuvant), pembrolizumab, losartan, aspirin, and chemotherapy of physician's choice

Study Record Dates

• First Submitted: August 7, 2026
• First Posted: August 13, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: August 13, 2026

Record last verified: 2026-08

Locations

US (1)