Breast CancerPhase 2NCT04373031
Pembrolizumab, IRX-2, and Chemotherapy in Triple Negative Breast Cancer
A Phase 2 study testing Pembrolizumab and IRX 2 in people with Breast Cancer and Breast Neoplasms, run by Providence Health & Services at 1 site in United States.
Trial summary
This is a Phase II, randomized, open-label trial to evaluate the clinical and immunologic activity of pembrolizumab plus chemotherapy when combined with various immunotherapy induction regimens as neoadjuvant therapy for triple negative breast cancer (TNBC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Breast Neoplasms
- What is being tested?
- Pembrolizumab and IRX 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Dec 2020to Dec 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
- Be a male or female subject greater than or equal to 18 years of age on day of signing informed consent.
- Have locally confirmed TNBC, as defined by the most recent ASCO/CAP guidelines.
- Have previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per the current AJCC Version 8 staging criteria for breast cancer staging criteria as assessed by the investigator based on radiological and/or clinical assessment:
- T1c, N1-N2
- T2, N0-N2
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- T3, N0-N2
- T4a-d, N0-N2 Note: bilateral tumors (i.e., synchronous cancers in both breasts) and/or multi-focal (i.e., 2, separate lesions in the same quadrant)/multi-centric (i.e., 2 separate lesions in different quadrants) tumors are allowed, as well as inflammatory breast cancer, and the tumor with the most advanced T stage should be used to assess the eligibility.
- Provide a core needle biopsy consisting of at least 1 separate tumor-bearing cores from the primary tumor at screening for translational research (archival is acceptable if sufficient tumor is available; slides are acceptable if at least 15 are available)
- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 14 days of treatment initiation.
- Demonstrate adequate organ function. All screening labs should be performed within 14 days of treatment initiation.
- Have left ventricular ejection fraction (LVEF) of ≥50% or ≥ institution lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening.
- Males and female subjects of childbearing potential (Section 5.7.2 - Contraception) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 12 months after the last dose of study medication for subjects who have received cyclophosphamide, and 6 months after the last dose of study medication for subjects who did not.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- (Female subject of childbearing potential) Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or borderline a serum pregnancy test will be required.
Who cannot join
- Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) or has previously participated in MK-3475 clinical trials.
- Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
- Note: subject should be excluded if he/she received an investigational agent with anti-cancer or anti-proliferative intent within the last 12 months.
- Has received a live vaccine within 30 days of the first dose of study treatment.
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- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines, and are not allowed.
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has significant cardiovascular disease, such as:
- History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months
- Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA class III or IV
- Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might expose the subject to risk by participating in the trial, confound the results of the trial, or interfere with the subject's participation for the full duration of the trial in the opinion of the Investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial in the opinion of the Investigator.
- Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 12 months after the last dose of trial treatment for subjects who have received cyclophosphamide, and for 6 months after the last dose of study medication for subjects who have not.
- Has a known hypersensitivity to the components of the study therapy or its analogs.
- Has a known history of active TB (Bacillus Tuberculosis).
- Allergy to ciprofloxacin (or other quinolones).
Trial locations and contacts
1 site in 1 country.
United States1 site
Providence Portland Medical Center
Portland, Oregon, 97213
About this study
Official title: Induction Immunotherapy to Promote Immunologic Priming and Enhanced Response to Neoadjuvant Pembrolizumab + Chemotherapy in Triple Negative Breast Cancer (TNBC)
This is a Phase II, randomized, open-label trial to evaluate the clinical and immunologic activity of pembrolizumab plus chemotherapy when combined with various immunotherapy induction regimens as neoadjuvant therapy for triple negative breast cancer (TNBC).
Read the detailed description
This is a Phase II, randomized, open-label trial to evaluate the clinical and immunologic activity of pembrolizumab plus chemotherapy when combined with various immunotherapy induction regimens as neoadjuvant therapy for triple negative breast cancer (TNBC).
A commonly used standard neoadjuvant regimen for TNBC is a weekly taxane (e.g., paclitaxel 80mg/m2) for 12 weeks followed by an anthracycline (e.g., doxorubicin 60 mg/m2 plus cyclophosphamide at 600 mg/m2 [AC]) every 3 weeks (Q3W) for 4 cycles.
The chemotherapy regimen included in this study is built upon the aforementioned regimen. Pembrolizumab in combination with this regimen will be studied as part of a multi-arm study that randomizes subjects to receive:
- Control Arm: (Pembro + ACT): Pembrolizumab induction (single-dose 200mg IV), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery.
- Arm A: (Pembro + IRX-2 + ACT): Pembrolizumab (single-dose 200mg IV) + cyclophosphamide (single-dose 300 mg/m2 IV) + IRX-2 induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by IRX-2 re-induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery.
- Subsequent induction therapy arms are to be included in protocol amendments. Note: 1 cycle = 21 days
- Conditions
- Breast Cancer, Breast Neoplasms
- Being tested
- Pembrolizumab, IRX 2
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called KEYTRUDA
Pembrolizumab is a humanized anti-PD-1 mAb of the IgG4/kappa isotype with a stabilizing S228P sequence alteration in the Fc region.
IRX 2Drug
IRX-2, is a cell-derived biologic with multiple active cytokine components that acts on multiple cell types of the immune system including T cells, dendritic cells and natural killer cells.
| Study group | Role | What they receive |
|---|---|---|
| Control | Experimental | Control Arm: (Pembro + ACT): Pembrolizumab induction (single-dose 200mg IV), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery. Receives: Drug: Pembrolizumab |
| Arm A | Experimental | • Arm A: (Pembro + IRX-2 + ACT): Pembrolizumab (single-dose 200mg IV) + cyclophosphamide (single-dose 300 mg/m2 IV) + IRX-2 induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by IRX-2 re-induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery. Receives: Drug: Pembrolizumab; Drug: IRX 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR) Rate (ypT0/Tis ypN0)
Number of patients who showed pCR post surgery. pCR rate (ypT0/Tis ypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy per the current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.
Measured: Following definitive surgery, approximately 9 months.
Secondary outcomes (2)
Safety and Tolerability Profile as Assessed by CTCAE v5.0
Number of serious adverse events (SAE) reported by patients attributed to study drugs.
Measured: Cycle 1, Day 1 through safety follow-up visit, approximately 9 months.
Percent Change in Tumor Infiltrating Lymphocytes (TIL) Quantity Changes
Evaluate increase in tumor infiltrating lymphocyte by H\&E (comparing diagnostic biopsy to post-induction biopsy). Tumor infiltrating lymphocytes will be assessed by the San Antonio stromal TIL criteria.
Measured: Following definitive surgery, approximately 9 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2020
- Study start30 Dec 2020
- Primary completion8 Jul 2023
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Brooklyn ImmunoTherapeutics, LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04373031
- Sponsor's protocol ID
- 2019000486
- Status last verified
- Apr 2026
- First submitted
- 28 Apr 2020
- Last updated
- 24 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction Immunotherapy to Promote Immunologic Priming and Enhanced Response to Neoadjuvant Pembrolizumab + Chemotherapy in Triple Negative Breast Cancer (TNBC)
- ClinicalTrials.gov ID
- NCT04373031
- Acronym / sponsor ID
- 2019000486
- Conditions
- Breast Cancer, Breast Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Brooklyn ImmunoTherapeutics, LLC
- Study start
- 30 Dec 2020 (actual)
- Primary completion
- 8 Jul 2023 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 4 May 2020 (actual)
- Results
- Posted 2 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II, randomized, open-label trial to evaluate the clinical and immunologic activity of pembrolizumab plus chemotherapy when combined with various immunotherapy induction regimens as neoadjuvant therapy for triple negative breast cancer (TNBC).
Detailed description
This is a Phase II, randomized, open-label trial to evaluate the clinical and immunologic activity of pembrolizumab plus chemotherapy when combined with various immunotherapy induction regimens as neoadjuvant therapy for triple negative breast cancer (TNBC).
A commonly used standard neoadjuvant regimen for TNBC is a weekly taxane (e.g., paclitaxel 80mg/m2) for 12 weeks followed by an anthracycline (e.g., doxorubicin 60 mg/m2 plus cyclophosphamide at 600 mg/m2 [AC]) every 3 weeks (Q3W) for 4 cycles.
The chemotherapy regimen included in this study is built upon the aforementioned regimen. Pembrolizumab in combination with this regimen will be studied as part of a multi-arm study that randomizes subjects to receive:
- Control Arm: (Pembro + ACT): Pembrolizumab induction (single-dose 200mg IV), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery.
- Arm A: (Pembro + IRX-2 + ACT): Pembrolizumab (single-dose 200mg IV) + cyclophosphamide (single-dose 300 mg/m2 IV) + IRX-2 induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by IRX-2 re-induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery.
- Subsequent induction therapy arms are to be included in protocol amendments. Note: 1 cycle = 21 days
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Experimental | Drug: PembrolizumabControl Arm: (Pembro + ACT): Pembrolizumab induction (single-dose 200mg IV), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery. |
| Arm A | Experimental | Drug: Pembrolizumab, Drug: IRX 2• Arm A: (Pembro + IRX-2 + ACT): Pembrolizumab (single-dose 200mg IV) + cyclophosphamide (single-dose 300 mg/m2 IV) + IRX-2 induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by IRX-2 re-induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
- Be a male or female subject greater than or equal to 18 years of age on day of signing informed consent.
- Have locally confirmed TNBC, as defined by the most recent ASCO/CAP guidelines.
- Have previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per the current AJCC Version 8 staging criteria for breast cancer staging criteria as assessed by the investigator based on radiological and/or clinical assessment:
- Provide a core needle biopsy consisting of at least 1 separate tumor-bearing cores from the primary tumor at screening for translational research (archival is acceptable if sufficient tumor is available; slides are acceptable if at least 15 are available)
Key exclusion criteria (22 listed)
- Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) or has previously participated in MK-3475 clinical trials.
- Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
- Note: subject should be excluded if he/she received an investigational agent with anti-cancer or anti-proliferative intent within the last 12 months.
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 |
|---|---|---|
| PembrolizumabAlso: KEYTRUDAPembrolizumab is a humanized anti-PD-1 mAb of the IgG4/kappa isotype with a stabilizing S228P sequence alteration in the Fc region. | Drug | Arm A, Control |
| IRX 2IRX-2, is a cell-derived biologic with multiple active cytokine components that acts on multiple cell types of the immune system including T cells, dendritic cells and natural killer cells. | Drug | Arm A |
Primary outcome
Pathological Complete Response (pCR) Rate (ypT0/Tis ypN0)
Time frame: Following definitive surgery, approximately 9 months.
Number of patients who showed pCR post surgery. pCR rate (ypT0/Tis ypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy per the current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.
2 secondary outcomes
Safety and Tolerability Profile as Assessed by CTCAE v5.0
Time frame: Cycle 1, Day 1 through safety follow-up visit, approximately 9 months.
Percent Change in Tumor Infiltrating Lymphocytes (TIL) Quantity Changes
Time frame: Following definitive surgery, approximately 9 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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. This study is not recruiting at the moment.
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 2 study testing Pembrolizumab and IRX 2 in people with Breast Cancer and Breast Neoplasms, run by Providence Health & Services 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 15 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 24 Apr 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 2 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Pathological Complete Response (pCR) Rate (ypT0/Tis ypN0) (time frame: Following definitive surgery, approximately 9 months.). 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 24 Apr 2026.