Triple-Negative Breast Cancer (TNBC)Phase 1/2NCT07762703
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
A Phase 1/2 study testing BreakVax, Ipilimumab 2.5 mg and Pembrolizumab in people with Triple-Negative Breast Cancer (TNBC), run by BreakBio Corp at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Triple-Negative Breast Cancer (TNBC)
- What is being tested?
- BreakVax, Ipilimumab 2.5 mg and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2026to Sep 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
- Albumin: ≥ 3.4 g/dL
- Serum Magnesium: ≥ 1.7 mg/dL
- Pulse oximetry ≥ 95% on room air
- Provision of consent for on-treatment biopsy (compulsory) and post-treatment biopsy (optional).
- Both male and female patients enrolled in this trial must agree to use effective contraception during the course of the trial and for at least 3 months after discontinuing study treatment. Patients and/or partners who are surgically sterile or postmenopausal are exempt from this requirement.
- Negative pregnancy test ≤ 7 days prior to day one of cycle 1, for women of childbearing potential only.
- Life expectancy > 6 months
- Willing and able to provide informed consent
Who cannot join
- 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.
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- 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.
- A serious local infection (e.g. cellulitis, abscess) or systemic infection (e.g. pneumonia, septicemia) which requires systemic antibiotic treatment within 4 weeks prior to the first dose of study medication.
- Receiving coumarin-derived anticoagulants.
- Unable or unwilling to withhold or discontinue any prohibited or restricted medications/ procedures for the specified windows during the study.
- Inability or refusal to comply with the protocol or with the clinical trial procedures
- If female, pregnant or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test prior to starting treatment.
- Chronic intake of drugs that lead to known interference with metabolism through strong Cytochrome P450 3A4 (CYP3A4) interaction: e.g. Rifampicin, Rifabutin, Clarithromycin, Telithromycin, Ketoconazole, Itraconazole, Fluconazole, Hypericum perforatum (St. John's Wort /Johanniskraut) or any strong CYP3A4 inducing or inhibiting drug (Note: participants in this study should avoid consuming grapefruit or grapefruit-containing products during the duration of the study, including the screening phase, treatment period, and follow-up period.)
- Uncontrolled hypertension defined as persistent systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg despite current therapy.
- Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months before the start of study medication. Active pulmonary emboli or deep vein thrombosis that are significant or not adequately controlled on anticoagulation regimen
- Any hemorrhage or bleeding event ≥ National Cancer Institute - Common terminology criteria for adverse events (NCI-CTCAE) Grade 3 within 28 days prior to the start of study medication
- History of other invasive cancer within 2 years prior to enrollment, except for treated non-melanoma skin cancer
- Known DNA Polymerase Epsilon (POLE) mutations
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Miami Herbert Wertheim Cancer Institute
Miami, Florida, 33176
Manmeet Ahluwalia, MD, MBA, FASCO
Reshma L Mahtani, DO
About this study
Official title: Phase 1/2 Trial of a Combination Immunotherapy Treatment for Solid Tumors Including BreakVax ImmunoTreatment (Designed and Manufactured Per Patient), Chemotherapy and Anti PD-1 Therapy
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:
Read more
- Low-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming;
- Pembrolizumab to mitigate PD-1-mediated T-cell exhaustion and sustain effector function;
- Standard-of-care chemotherapy, which may promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment; and
- 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.
The study consists of two components: a Safety Lead-in Cohort and a randomized combination therapy cohort. The Safety Lead-in Cohort is designed to evaluate safety and tolerability of the study combination and to characterize dose-limiting toxicities (DLTs). The randomized combination therapy cohort portion is designed to evaluate the antitumor activity of the study combination compared with standard-of-care (SOC) chemotherapy of physician's choice, as measured by objective response rate (ORR), and to evaluate disease control rate (DCR) in patients who receive the study combination following progression on SOC chemotherapy.
Read the detailed description
Study Design Overview
Patient Timeline:
- Patients will start first-line therapy with ADC (not yet enrolled on this study)
- Patients provide tumor tissue (frozen in AllProtect) to BreakBio for analysis in the first 10 weeks of ADC therapy (patients sign 1st consent to share tumor tissue with BreakBio). Biopsy can be from primary site or metastatic site. BreakBio will provide detailed reports from DNA and RNA analysis to treating physician (not yet enrolled on this study)
- Patients who progress on first-line ADC therapy are pre-screened for this study (not yet enrolled on this study)
- Patients who pass the pre-screening for this study start 2 cycles of induction chemotherapy of physician's choice. Treating physician informs BreakBio to begin manufacturing BreakVax (not yet enrolled on this study)
- After 2 cycles of induction chemotherapy, patients are screened for eligibility for this study. If BreakVax manufacturing is delayed, patients should complete a 3rd cycle of induction chemotherapy before screening. Patients are only eligible if they do not experience progression during these induction chemotherapy cycles (not yet enrolled on this study)
- Patients who pass screening will sign 2nd consent to enroll in study (enrolled in study)
- The first 3 patients, who are enrolled on Substudy A or B or a combination of both, will comprise the Safety Lead-in Cohort (no randomization, as detailed below) (enrolled in study)
- After the Safety Lead-in Cohort is complete, further patients will be randomized to either the BreakVax Arm or the Delayed BreakVax Arm as detailed below (enrolled in study)
Safety Lead-in Cohort The first three patients, who are enrolled on Substudy A or B or a combination of both, will comprise a Safety Lead-in Cohort to characterize dose-limiting toxicities (DLTs) and early safety. For Substudy A, the treatment cycle is 21 days, however, the DLT evaluation period will be 28 days. These patients will receive 2 cycles of induction chemotherapy (Cycles -1 and -2), followed by a 28 day DLT evaluation period (21 days of Cycle 1 and 7 days of Cycle 2).
- Treatment: In the first 21 days (Cycle 1) formulated BreakVax and low-dose subcutaneous ipilimumab (administered locally at the injection site as a local dendritic cell adjuvant to enhance T-cell priming) will be administered without chemotherapy or other combination drugs. Then, patients will proceed to Cycle 2 of the BreakVax Arm, where they will receive BreakVax and all combination drugs.
- Monitoring: Patients will be monitored over 28 days (21 days with BreakVax and low-dose ipilimumab alone, and then the first 7 days of Cycle 2 of the BreakVax Arm, where they will receive BreakVax and all combination drugs) for DLTs.
- Following completion of the DLT evaluation period (28-days), patients will continue with Cycle 2 of the BreakVax Arm. After the three patients in the Safety Lead-in Cohort have completed the DLT evaluation period (either as part of Substudy A or B or a combination of both), the randomized phase of the study will begin.
If ≥2 DLTs are observed among the initial 3 patients, an additional 3 patients, who will be enrolled on Substudy A or B or a combination of both, will be enrolled in the Safety Lead-in Cohort. If ≥3 DLTs are observed among the 6 patients, continuation of the study will be reviewed by the Safety Monitoring Committee (SMC), which may recommend study termination based on safety findings.
Randomized Combination Therapy Cohort
Following completion of the Safety Lead-in Cohort, 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.
Treatment Schedule:
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 21-day cycle. Steroid-containing premedications are not permitted (see Disallowed Concomitant Medications listed below).
- 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.
Delayed BreakVax Arm 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.
- Conditions
- Triple-Negative Breast Cancer (TNBC)
- Being tested
- BreakVax, Ipilimumab 2.5 mg, Pembrolizumab, Standard-of-care chemotherapy, Losartan and aspirin
- Keywords
- Triple Negative Breast Cancer, PD-L1 negative, gBRCA negative, Locally Advanced, Unresectable, Metastatic
- Medical subject headings
- Triple Negative Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BreakVaxDrug
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
Ipilimumab 2.5 mgDrug
A local dendritic cell adjuvant injected adjacent to the BreakVax site to promote antigen presentation and T-cell priming
PembrolizumabDrug
To mitigate PD-1-mediated T-cell exhaustion and sustain effector function
Standard-of-care chemotherapyDrug
May promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment
Losartan and aspirinDrug
Have been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Standard-of-care chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: up to 24 Months
Adverse events
Number and percentage of participants experiencing treatment-emergent adverse events
Measured: up to 24 Months
Secondary outcomes (9)
Change in Tumor T-cell Infiltration Between Pre-treatment and On-treatment Biopsies
Tumor T-cell infiltration will be compared between the pre-treatment tumor biopsy and the on-treatment tumor biopsy obtained at approximately Cycle 3 (after imaging).
Measured: Baseline to approximately Cycle 3 after imaging
Progression-Free Survival (PFS) per RECIST v1.1
Progression-free survival is defined as the time from the start of study treatment to disease progression according to RECIST v1.1 or death, whichever occurs first, as assessed by a central independent review committee (IRC).
Measured: From start of study treatment to disease progression or death, up to 2 years
Duration of Response (DoR) per RECIST v1.1
Duration of response is defined for participants who achieve a complete response (CR) or partial response (PR) as the time from the first assessment at which criteria for CR or PR are met until the first objectively documented disease progression according to RECIST v1.1, as assessed by a central independent review committee (IRC).
Measured: From first documented CR or PR to disease progression, up to 2 years
Clinical Benefit Rate (CBR) per RECIST v1.1
Percentage of participants with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) lasting at least 12 weeks according to RECIST v1.1, as assessed by a central independent review committee (IRC).
Measured: From start of study treatment through disease progression, up to 2 years
Objective Response Rate (ORR) per RECIST v1.1
Percentage of participants with measurable disease who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by a central independent review committee (IRC).
Measured: From start of study treatment through disease progression, up to 2 years
Immune-related Progression-Free Survival (irPFS) per iRECIST
Immune-related progression-free survival is defined as the time from the start of study treatment to confirmed progressive disease according to iRECIST or death, whichever occurs first. Unconfirmed progression does not constitute a progression event until progression is confirmed according to iRECIST.
Measured: From start of study treatment to confirmed disease progression or death, up to 2 years
Incidence of Pseudoprogression per iRECIST
Percentage of participants who experience pseudoprogression according to iRECIST, defined as an apparent increase in tumor burden or appearance of new lesions that is not subsequently confirmed as true disease progression on follow-up assessment.
Measured: From start of study treatment through disease progression, up to 2 years
Stable Disease for at Least 12 Weeks per iRECIST
Percentage of participants who have stable disease according to iRECIST lasting at least 12 weeks, using the protocol-specified assessment window of 12 weeks ±1 week.
Measured: From start of study treatment through disease progression, up to 2 years
Overall Survival (OS)
Overall survival is defined as the time from randomization to death from any cause. Overall survival will be analyzed descriptively because of the crossover design.
Measured: From randomization to death, up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2030 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple-Negative Breast Cancer (TNBC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BreakBio Corp
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Miami Cancer Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07762703
- Sponsor's protocol ID
- BreakBio-3 Substudy A
- Status last verified
- Aug 2026
- First submitted
- 7 Aug 2026
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Trial of a Combination Immunotherapy Treatment for Solid Tumors Including BreakVax ImmunoTreatment (Designed and Manufactured Per Patient), Chemotherapy and Anti PD-1 Therapy
- ClinicalTrials.gov ID
- NCT07762703
- Acronym / sponsor ID
- BreakBio-3 Substudy A
- Conditions
- Triple-Negative Breast Cancer (TNBC)
- Keywords
- Triple Negative Breast Cancer, PD-L1 negative, gBRCA negative, Locally Advanced, Unresectable, Metastatic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- BreakBio CorpIndustry (pharma, biotech, devices)
- Collaborators
- Miami Cancer Institute
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2030 (estimated)
- Study completion
- Sep 2030 (estimated)
- First posted
- 13 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Low-dose subcutaneous ipilimumab at the injection site as a dendritic cell adjuvant to enhance local dendritic cell-mediated T-cell priming;
- Pembrolizumab to mitigate PD-1-mediated T-cell exhaustion and sustain effector function;
- Standard-of-care chemotherapy, which may promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment; and
- 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.
The study consists of two components: a Safety Lead-in Cohort and a randomized combination therapy cohort. The Safety Lead-in Cohort is designed to evaluate safety and tolerability of the study combination and to characterize dose-limiting toxicities (DLTs). The randomized combination therapy cohort portion is designed to evaluate the antitumor activity of the study combination compared with standard-of-care (SOC) chemotherapy of physician's choice, as measured by objective response rate (ORR), and to evaluate disease control rate (DCR) in patients who receive the study combination following progression on SOC chemotherapy.
Detailed description
Study Design Overview
Patient Timeline:
- Patients will start first-line therapy with ADC (not yet enrolled on this study)
- Patients provide tumor tissue (frozen in AllProtect) to BreakBio for analysis in the first 10 weeks of ADC therapy (patients sign 1st consent to share tumor tissue with BreakBio). Biopsy can be from primary site or metastatic site. BreakBio will provide detailed reports from DNA and RNA analysis to treating physician (not yet enrolled on this study)
- Patients who progress on first-line ADC therapy are pre-screened for this study (not yet enrolled on this study)
- Patients who pass the pre-screening for this study start 2 cycles of induction chemotherapy of physician's choice. Treating physician informs BreakBio to begin manufacturing BreakVax (not yet enrolled on this study)
- After 2 cycles of induction chemotherapy, patients are screened for eligibility for this study. If BreakVax manufacturing is delayed, patients should complete a 3rd cycle of induction chemotherapy before screening. Patients are only eligible if they do not experience progression during these induction chemotherapy cycles (not yet enrolled on this study)
- Patients who pass screening will sign 2nd consent to enroll in study (enrolled in study)
- The first 3 patients, who are enrolled on Substudy A or B or a combination of both, will comprise the Safety Lead-in Cohort (no randomization, as detailed below) (enrolled in study)
- After the Safety Lead-in Cohort is complete, further patients will be randomized to either the BreakVax Arm or the Delayed BreakVax Arm as detailed below (enrolled in study)
Safety Lead-in Cohort The first three patients, who are enrolled on Substudy A or B or a combination of both, will comprise a Safety Lead-in Cohort to characterize dose-limiting toxicities (DLTs) and early safety. For Substudy A, the treatment cycle is 21 days, however, the DLT evaluation period will be 28 days. These patients will receive 2 cycles of induction chemotherapy (Cycles -1 and -2), followed by a 28 day DLT evaluation period (21 days of Cycle 1 and 7 days of Cycle 2).
- Treatment: In the first 21 days (Cycle 1) formulated BreakVax and low-dose subcutaneous ipilimumab (administered locally at the injection site as a local dendritic cell adjuvant to enhance T-cell priming) will be administered without chemotherapy or other combination drugs. Then, patients will proceed to Cycle 2 of the BreakVax Arm, where they will receive BreakVax and all combination drugs.
- Monitoring: Patients will be monitored over 28 days (21 days with BreakVax and low-dose ipilimumab alone, and then the first 7 days of Cycle 2 of the BreakVax Arm, where they will receive BreakVax and all combination drugs) for DLTs.
- Following completion of the DLT evaluation period (28-days), patients will continue with Cycle 2 of the BreakVax Arm. After the three patients in the Safety Lead-in Cohort have completed the DLT evaluation period (either as part of Substudy A or B or a combination of both), the randomized phase of the study will begin.
If ≥2 DLTs are observed among the initial 3 patients, an additional 3 patients, who will be enrolled on Substudy A or B or a combination of both, will be enrolled in the Safety Lead-in Cohort. If ≥3 DLTs are observed among the 6 patients, continuation of the study will be reviewed by the Safety Monitoring Committee (SMC), which may recommend study termination based on safety findings.
Randomized Combination Therapy Cohort
Following completion of the Safety Lead-in Cohort, 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.
Treatment Schedule:
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 21-day cycle. Steroid-containing premedications are not permitted (see Disallowed Concomitant Medications listed below).
- 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.
Delayed BreakVax Arm 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| BreakVax Arm | Experimental | Drug: BreakVax, Drug: Ipilimumab 2.5 mg, Drug: Pembrolizumab, Drug: Standard-of-care chemotherapy, Drug: Losartan and aspirinA 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 |
| Delayed BreakVax Arm | Active comparator | Drug: Standard-of-care chemotherapyPatients 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 |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BreakVaxBreakVax (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 | Drug | BreakVax Arm |
| Ipilimumab 2.5 mgA local dendritic cell adjuvant injected adjacent to the BreakVax site to promote antigen presentation and T-cell priming | Drug | BreakVax Arm |
| PembrolizumabTo mitigate PD-1-mediated T-cell exhaustion and sustain effector function | Drug | BreakVax Arm |
| Standard-of-care chemotherapyMay promote immunogenic cell death, increase antigen release and modulate the tumor microenvironment | Drug | BreakVax Arm, Delayed BreakVax Arm |
| Losartan and aspirinHave been associated in preclinical and translational studies with modulation of stromal architecture, vascular normalization, and reduction of tumor-associated immunosuppressive signaling | Drug | BreakVax Arm |
Primary outcome
Immune-related Objective Response Rate (irORR) per iRECIST Assessed by Independent Review Committee
Time frame: 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
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.
Disease Control Rate (DCR) Following Crossover to BreakVax Combination Treatment
Time frame: From initiation of BreakVax combination treatment after crossover through subsequent disease progression, up to 2 years
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.
Percentage of patients for whom BreakVax is successfully manufactured
Time frame: up to 24 Months
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.
Adverse events
Time frame: up to 24 Months
Number and percentage of participants experiencing treatment-emergent adverse events
9 secondary outcomes
Change in Tumor T-cell Infiltration Between Pre-treatment and On-treatment Biopsies
Time frame: Baseline to approximately Cycle 3 after imaging
Progression-Free Survival (PFS) per RECIST v1.1
Time frame: From start of study treatment to disease progression or death, up to 2 years
Duration of Response (DoR) per RECIST v1.1
Time frame: From first documented CR or PR to disease progression, up to 2 years
Clinical Benefit Rate (CBR) per RECIST v1.1
Time frame: From start of study treatment through disease progression, up to 2 years
Objective Response Rate (ORR) per RECIST v1.1
Time frame: From start of study treatment through disease progression, up to 2 years
Immune-related Progression-Free Survival (irPFS) per iRECIST
Time frame: From start of study treatment to confirmed disease progression or death, up to 2 years
Incidence of Pseudoprogression per iRECIST
Time frame: From start of study treatment through disease progression, up to 2 years
Stable Disease for at Least 12 Weeks per iRECIST
Time frame: From start of study treatment through disease progression, up to 2 years
Overall Survival (OS)
Time frame: From randomization to death, up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BreakVax, Ipilimumab 2.5 mg and Pembrolizumab in people with Triple-Negative Breast Cancer (TNBC), run by BreakBio Corp at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune-related Objective Response Rate (irORR) per iRECIST Assessed by Independent Review Committee (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.