HER2-addicted Breast CancerPhase 2RTPNCT07772245

Trial of Retifanlimab With Trastuzumab and Pertuzumab Combination in HER2-Addicted Breast Cancer

A Phase 2 study testing Retifanlimab, Trastuzumab (Herceptin) and Pertuzumab in people with HER2-addicted Breast Cancer, run by Polly A. Niravath, MD.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: HER2-addicted Breast Cancer
What is being tested?: Retifanlimab, Trastuzumab (Herceptin) and Pertuzumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: No sites listed yet
Study dates: 31 Dec 2026to 31 Dec 2032
Phase: Phase 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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients are eligible to be included in the trial only if all of the following criteria apply:
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) will be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Male and female aged >18 years at the time of study entry. HR-positive patients are eligible because eligibility is driven by the biologic enrichment criteria above; HR status will be recorded and analyzed as a prespecified subgroup.
All breast cancers must be HER2+ (IHC 3+ or FISH >=2) and HER2- addicted(Low Relapse score on HER2Dx assay or PDL >10%. ER+ HER2+ cancers are allowed. Patients who are progesterone receptor positive or negative will be eligible to participate in the study.
Primary tumor greater than 1 cm diameter and <=5cm, measured by clinical examination and mammography or echography.
T1-T2, N0-N1 tumors

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Bilateral breast cancers that individually meet eligibility criteria are allowed.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 as of consent date .
Life expectancy >6 months.
Adequate organ and marrow function as defined below:
Hemoglobin ≥10.0 g/dL with no blood transfusion in the past 28 days
Absolute neutrophil count ≥1.5 × 109/L
Platelet count ≥100 × 109/L
Serum total bilirubin ≤1 × institutional upper limit of normal (ULN; In the case of known Gilbert's syndrome, a higher serum total bilirubin [< 1.5 × ULN] is allowed),
Aspartate transaminase/alanine transaminase ≤2.5 × institutional ULN
Alkaline phosphatase ≤1.5 × institutional ULN
Creatinine ≤1.5 mg/dL
Baseline left ventricular ejection fraction ≥50%, as measured by multigated acquisition (MUGA) scan or echocardiogram (ECHO).
Evidence of postmenopausal status or negative serum pregnancy test for premenopausal female patients. Negative serum β-human chorionic gonadotropin pregnancy test within 7 days prior to the first dose of study treatment for premenopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
Women <50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
Willing to provide biopsy tissues as required by the study. - Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.

Who cannot join

Patients are excluded from the trial if any of the following criteria apply:
Participation in another clinical study with an investigational product within 28 days prior to the first dose of study treatment.
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
Unresolved or unstable adverse events (AEs) Grade 3 from prior administration of another investigational drug.
Any concurrent chemotherapy, radiation therapy, immunotherapy, or biologic therapy for cancer treatment.
Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment.

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History of allogeneic bone marrow/stem, cell or solid organ transplantation.
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the study physician
History of active primary immunodeficiency.
Active infection including tuberculosis (clinical evaluation that includes clinical history, physical exam and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of hepatitis B surface antigen [HBsAg]) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
Steroids as premedication for hypersensitivity reactions
Female patients who are pregnant or breastfeeding or patients of reproductive potential who are not willing to employ effective birth control from screening to 7 months after the last dose of study treatment.
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
Patients with a mean QT interval of greater than or equal to 470ms calculated from 3 screening EKGs.
Patients with underlying cardiovascular conditions that have recently undergone interventions including: cardiac ventricular arrhythmia requiring medication, history of second or third degree AV blocks, myocardial infarction with the previous year, congestive heart failure, and unstable angina.
Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis at the time of consent.
Palliative radiation therapy administered within 1 week before the first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months before the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities (to Grade ≤ 1 or baseline), must not require corticosteroids for this purpose, and must not have had radiation pneumonitis.
Has received a live vaccine within 28 days before the planned start of study treatment Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, varicella-zoster (chickenpox), yellow fever, rabies, BCG, and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines are live, attenuated vaccines and are not allowed. COVID vaccines are allowed.

About this study

Official title: Phase II Trial of Retifanlimab With Trastuzumab and Pertuzumab Combination in HER2-Addicted Breast Cancer

The goal of this Clinical Trial is to find out how well 3 medicines (retifanlimab, trastuzumab and pertuzumab) work at treating HER2-positive breast cancer in Male and female patients, 18 or older. The main question aims to determine the pathologic response rate [residual cancer burden (RCB)- 0] in the breast and lymph nodes after 6 cycles of retifanlimab, trastuzumab and pertuzumab in patients with HER2-addicted breast cancer. Participants will will have at least 6 cycles of the study drug, assuming the participant is responding to and tolerating the treatment well. Every cycle will last about 21 days.

Read the detailed description

This is a Phase II study evaluating the efficacy of retifanlimab, trastuzumab and pertuzumab (RTP) in HER2- addicted breast cancer. Male and female patients, aged ≥18 years, with HER2-addicted breast cancer (low relapse score on HER2Dx assay or PDL >10%) will be eligible to participate in the trial. At least 30 cancer patients will be enrolled in the trial. Based on previous experience, approximately 75% of patients who had a low HER2Dx® survival score or had a PDL1-CPS score >10% achieved a pathologic complete response (pCR) after neoadjuvant combination treatment with immunotherapy and HER2-directed antibodies (NCT03820141). Therefore, in the current trial, patients who meet this criteria will receive 6 cycles of retifanlimab, trastuzumab and pertuzumab (21-days cycles).

Patients will undergo breast MRI and physical exam after completion of 6 cycles of RTP therapy. Patients who have a radiologic and clinical complete response will have surgery and will then receive the adjuvant RTP for 11 cycles. Patients who have not had a complete clinical and radiographic response will have a biopsy to prove pathologic residual disease. These patients will then receive standard-of-care (SOC) neoadjuvant chemotherapy per treating physician's discretion. Patients who are estrogen receptor (ER) positive and HER2+ will also receive aromatase inhibitor (+/- ovarian suppression, depending on menopausal status) with the RTP study treatment. Correlative studies will include tissue and blood-based molecular and genetic biomarkers of response and resistance to the regimen. Study follow-ups will be provided every 12 weeks, as per standard-of-care. The primary endpoint of the trial will be pathologic response rate (RCB- 0) in the breast and lymph nodes after 6 cycles of retifanlimab, trastuzumab and pertuzumab in patients with HER2- addicted breast cancer. We hypothesize that retifanlimab, trastuzumab and pertuzumab in patients with HER2-addicted breast cancer will have a pathologic complete response rate of 75%.

Conditions: HER2-addicted Breast Cancer
Being tested: Retifanlimab, Trastuzumab (Herceptin), Pertuzumab
Keywords: Retifanlimab, RTP, Low Relapse Score on HER2DX assay, PDL > 10%

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RetifanlimabDrug
375 mg administered as an IV infusion over 30 minutes Q3W.
Trastuzumab (Herceptin)Drug
Loading dose as 8 mg/kg IV infusion over 90 minutes; Subsequent doses as 6 mg/kg IV infusion over 30-90 minutes Q3W
PertuzumabDrug
Loading dose as 840 mg IV infusion over 60 minutes; Subsequent doses as 420 mg IV infusion over 30-60 minutes Q3W

Study groups in NCT07772245
Study group	Role	What they receive
Retifanlimab, Trastuzumab, and Pertuzumab	Experimental	Trastuzumab: Loading dose as 8 mg/kg IV infusion over 90 minutes; Subsequent doses as 6 mg/kg IV infusion over 30-90 minutes Q3W Pertuzumab: Loading dose as 840 mg IV infusion over 60 minutes; Subsequent doses as 420 mg IV infusion over 30-60 minutes Q3W Retifanlimab:375 mg administered as an IV infusion over 30 minutes Q3W. Receives: Drug: Retifanlimab; Drug: Trastuzumab (Herceptin); Drug: Pertuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Pathologic Response Rate
To determine the pathologic response rate [residual cancer burden (RCB)- 0] in the breast and lymph nodes after 6 cycles of retifanlimab, trastuzumab and pertuzumab in patients with HER2-addicted breast cancer.
Measured: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]

Secondary outcomes (5)

Estimate RCB rate based on patients tumor-infiltrating lymphocytes
To estimate RCB 0 and RCB 1 rate in patients whose tumors have < 10% and ≥ 10% tumor-infiltrating lymphocytes (TILs).
Measured: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]
Estimate RCB rate based on patients PD-L1 status
To estimate RCB 0 and RCB 1 rate in patients with PD-L1-positive (≥10% tumor or stroma) and PD-L1-negative tumors (<10% tumor or stroma).
Measured: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]
Disease-Free Survival (DFS) rate
To determine the 3-year disease-free survival (DFS) rate of retifanlimab, trastuzumab and pertuzumab in patients with HER2- addicted breast cancer (only for patients who achieve RCB 0 and RCB 1).
Measured: From enrollment until end of follow-up [4 years]
Safety and Toxicity of Retifanlimab, Trastuzumab, and Pertuzumab
To determine safety and toxicity of retifanlimab, trastuzumab and pertuzumab in patients with HER2- addicted breast cancer, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.
Measured: From time of enrollment until end of treatment [1 year]
Correlation between ctDNA and pCR
To determine whether early clearance of ctDNA correlates with pCR
Measured: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Dec 202631 Dec 2032

First posted19 Aug 2026
Study start31 Dec 2026 (estimated)
Primary completion31 Dec 2029 (estimated)
Study completion31 Dec 2032 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HER2-addicted 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07772245
Sponsor's protocol ID: PRO00044395 (HMCC-BR25-002)
Acronym: RTP
Status last verified: Aug 2026
First submitted: 6 Aug 2026
Last updated: 19 Aug 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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 II Trial of Retifanlimab With Trastuzumab and Pertuzumab Combination in HER2-Addicted Breast Cancer
ClinicalTrials.gov ID: NCT07772245
Acronym / sponsor ID: RTP / PRO00044395 (HMCC-BR25-002)
Conditions: HER2-addicted Breast Cancer
Keywords: Retifanlimab, RTP, Low Relapse Score on HER2DX assay, PDL > 10%
Phase: Phase 2
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 30 participants (estimated)
Lead sponsor: Polly A. Niravath, MDUniversity, hospital or other
Study start: 31 Dec 2026 (estimated)
Primary completion: 31 Dec 2029 (estimated)
Study completion: 31 Dec 2032 (estimated)
First posted: 19 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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Retifanlimab, Trastuzumab, and Pertuzumab	Experimental	Drug: Retifanlimab, Drug: Trastuzumab (Herceptin), Drug: PertuzumabTrastuzumab: Loading dose as 8 mg/kg IV infusion over 90 minutes; Subsequent doses as 6 mg/kg IV infusion over 30-90 minutes Q3W Pertuzumab: Loading dose as 840 mg IV infusion over 60 minutes; Subsequent doses as 420 mg IV infusion over 30-60 minutes Q3W Retifanlimab:375 mg administered as an IV infusion over 30 minutes Q3W.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

Patients are eligible to be included in the trial only if all of the following criteria apply:
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) will be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Male and female aged >18 years at the time of study entry. HR-positive patients are eligible because eligibility is driven by the biologic enrichment criteria above; HR status will be recorded and analyzed as a prespecified subgroup.
All breast cancers must be HER2+ (IHC 3+ or FISH >=2) and HER2- addicted(Low Relapse score on HER2Dx assay or PDL >10%. ER+ HER2+ cancers are allowed. Patients who are progesterone receptor positive or negative will be eligible to participate in the study.
Primary tumor greater than 1 cm diameter and <=5cm, measured by clinical examination and mammography or echography.

Key exclusion criteria (25 listed)

Participation in another clinical study with an investigational product within 28 days prior to the first dose of study treatment.
Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
Unresolved or unstable adverse events (AEs) Grade 3 from prior administration of another investigational drug.
Any concurrent chemotherapy, radiation therapy, immunotherapy, or biologic therapy for cancer treatment.
Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment.

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
Retifanlimab375 mg administered as an IV infusion over 30 minutes Q3W.	Drug	Retifanlimab, Trastuzumab, and Pertuzumab
Trastuzumab (Herceptin)Loading dose as 8 mg/kg IV infusion over 90 minutes; Subsequent doses as 6 mg/kg IV infusion over 30-90 minutes Q3W	Drug	Retifanlimab, Trastuzumab, and Pertuzumab
PertuzumabLoading dose as 840 mg IV infusion over 60 minutes; Subsequent doses as 420 mg IV infusion over 30-60 minutes Q3W	Drug	Retifanlimab, Trastuzumab, and Pertuzumab

Primary outcome

Pathologic Response Rate
Time frame: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]
To determine the pathologic response rate [residual cancer burden (RCB)- 0] in the breast and lymph nodes after 6 cycles of retifanlimab, trastuzumab and pertuzumab in patients with HER2-addicted breast cancer.

5 secondary outcomes

Estimate RCB rate based on patients tumor-infiltrating lymphocytes
Time frame: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]
Estimate RCB rate based on patients PD-L1 status
Time frame: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]
Disease-Free Survival (DFS) rate
Time frame: From enrollment until end of follow-up [4 years]
Safety and Toxicity of Retifanlimab, Trastuzumab, and Pertuzumab
Time frame: From time of enrollment until end of treatment [1 year]
Correlation between ctDNA and pCR
Time frame: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]

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: No

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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Retifanlimab, Trastuzumab (Herceptin) and Pertuzumab in people with HER2-addicted Breast Cancer, run by Polly A. Niravath, MD.

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 22 inclusion and 25 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.

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?

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?

Pathologic Response Rate (time frame: From time of enrollment to the 6th cycle (21 day cycles) of treatment [18 weeks]). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07772245.

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.