AzTrials
AzTrials

Breast CancerPhase 1NCT03032107

A Study Of Pembrolizumab In Combination With Trastuzumab-DM1

A Phase 1 study testing T-DM1 and Pembrolizumab in people with Breast Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This research study is studying a combination of drugs as a possible treatment for metastatic breast cancer. The interventions involved in this study are: Pembrolizumab Trastuzumab emtansine (also called T-DM1) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
T-DM1 and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesUnited States
Study dates
17 Feb 2017to 5 Dec 2024
Phase
Phase 1
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

  • Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease. Patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
  • Either the primary tumor and/or the metastasis must have been tested for ER, PR and HER2. Patient must have HER2+ breast cancer per ASCO CAP guidelines 2013.
  • Prior chemotherapy:
  • History of prior therapy with trastuzumab and a taxane, separately or in combination, is required.
  • Patients must have either received one line of prior therapy for metastatic breast cancer, or have developed a disease recurrence during or within 6 months after completing adjuvant therapy.
  • No prior treatment with T-DM1 is allowed.
Show all 34Show fewer
  • Last dose of chemotherapy must be at least 21 days prior to registration.
  • Prior biologic therapy:
  • --Patients must have discontinued all biologic or investigational therapy at least 21 days before registration.
  • Prior radiation therapy:
  • Patients may have received prior radiation therapy in either the metastatic or early-stage setting.
  • Radiation therapy must be completed at least 14 days prior to registration.
  • In the dose de-escalation cohort: Subjects must have evaluable disease. In the expansion cohort: Subjects must have at least one lesion that is not within a previously radiated field that is measurable on computerized tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST version 1.1. Bone lesions are not considered measurable by definition.
  • Age is ≥18 years.
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • Participants must have normal organ and marrow function as defined below:
  • absolute neutrophil count ≥1,500/μl
  • platelets ≥100,000/μl
  • hemoglobin ≥9 g/dL
  • total bilirubin ≤1.5mg/dL (≤2.0 in patients with known Gilberts syndrome)
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN. ≤5.0 × institutional ULN for patients with documented liver metastases.
  • albumin >2.5mg/dL
  • serum creatinine ≤1.5mg/dL or calculated GFR ≥60 mL/min
  • INR/PT ≤1.5 times ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • aPTT/PTT ≤1.5 times ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Participants enrolling in the dose expansion must have tissue that is amenable to biopsy and be willing to undergo a fresh tissue biopsy at baseline. Participants who undergo an attempted research biopsy procedure for the purpose of this protocol, and in whom inadequate tissue is obtained, are not required to undergo a repeat biopsy in order to continue on protocol.
  • The effects of pembrolizumab on the developing human fetus are unknown. For this reason and because tratuzumab, a component of T-DM1, is known to be teratogenic, women of child-bearing potential and men of childbearing potential must agree to use adequate contraception starting with the first dose of study therapy, for the duration of study participation, and for an additional 120 days after the last dose of study medication. Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the treating physician and principal investigator should be informed immediately.
  • While on the study, women should not breast-feed.
  • Subjects of childbearing potential are defined as those who have not been surgically sterilized and/or have had a menstrual period in the past year
  • Female subject of child-bearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Patients on bisphosphonates may continue receiving bisphosphonate therapy during study treatment.
  • Left ventricular ejection fraction (LVEF) must be within institutional limits of normal as assessed by echocardiogram or MUGA documented within 28 days prior to first dose of study drug.
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • The subject has received another investigational agent within 21 days of the first dose of study drug.
  • The subject has received prior pembrolizumab or any other anti-PD-1 , anti-PD-L1, or anti-PD-L2 therapy, or has participated in any prior studies involving pembrolizumab.
  • Pre-existing neuropathy greater than or equal to grade 2.
  • Hypersensitivity to pembrolizumab or T-DM1 or any of their excipients.
  • The subject has any history or evidence of active, non-infectious pneumonitis or interstitial lung disease.
  • Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with previously diagnosed brain metastases are eligible if they have completed treatment at least one month prior to trial therapy initiation, are neurologically stable with an absence of new neurological symptoms for at least 4 weeks prior to study entry, and have recovered from effects of radiotherapy or surgery. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥2 weeks before the first study drug. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician.
Show all 16Show fewer
  • Known carcinomatous meningitis.
  • The subject has an uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure (New York Heart Association Class III or IV; see Appendix B), active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, chronic liver or renal disease, or severe malnutrition.
  • Concurrent use of potent CYP3A4 inhibitors (see Appendix C), such as ketoconazole and erythromycin, should be avoided during the study treatment with T-DM1.
  • Active infection requiring intravenous antibiotics at cycle 1 day 1.
  • Individuals with a history of a second malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and non-melanoma cancer of the skin. Patients with other cancers diagnosed within the past 5 years and felt to be at low risk of recurrence should be discussed with the study sponsor to determine eligibility.
  • The subject has a medical condition that requires chronic systemic steroid therapy or any other form of immunosuppressive medication including disease modifiying agents, or has required such therapy in the last 2 years. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • The subject has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.
  • The participant is positive for Hepatitis B surface antigen, or Hepatitis C RNA.
  • Known HIV-positive participants. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections with bone marrow suppressive therapy, i.e. nab-paclitaxel. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • The subject has received a live vaccine within 28 days of planned start of study therapy. Note: seasonal influenza vaccines for infection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (i.e. Flu-Mist ®) are live attenuated vaccines, and are not allowed

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase 1b Study Of Pembrolizumab In Combination With Trastuzumab-DM1 In Metastatic HER2-Positive Breast Cancer

This research study is studying a combination of drugs as a possible treatment for metastatic breast cancer.

The interventions involved in this study are:

  • Pembrolizumab
  • Trastuzumab emtansine (also called T-DM1)
Read the detailed description

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved the combination of Pembrolizumab and T-DM1 for use in patients, including people with your type of cancer.

This study will determine what amount (or dose) of Pembrolizumab and of T-DM1 is safe for people to take and what effects, good or bad, this combination may have on participants and their disease.

The FDA has not approved Pembrolizumab for this specific disease but it has been approved in the United Sates for the treatment of other types of cancer.

The FDA has approved Trastuzumab emtansine (T-DM1) as a treatment option for this type of breast cancer

The combination of Pembrolizumab and T-DM1 is investigational. It is thought that together these drugs to help get the immune system to attack tumor cells and kill cancer cells that have the HER2 protein. However, it is not known if giving the two study drugs at the same time will have a better anti-cancer effect than giving each treatment on its own.

Conditions
Breast Cancer
Being tested
T-DM1, Pembrolizumab
Keywords
Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

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

  • T-DM1Drug

    Also called Trastuzumab emtansine

    -T-DM1 will be administered intravenousely in clinic on day 1 of each 3-week cycle

  • PembrolizumabDrug

    Also called Keytruda

    -Pembrolizumab will be administered intravenousely in clinic on day 1 of each 3-week cycle

Study groups in NCT03032107
Study groupRoleWhat they receive
Pembrolizumab Combine With Trastuzumab EmtansineExperimental* Pembrolizumab will be administered intravenousely in clinic on day 1 of each 3-week cycle * Pembrolizumab will be administered prior to T-DM1 administration * Pembrolizumab will be given at a predetermine dose * T-DM1 will be administered intravenousely in clinic on day 1 of each 3-week cycle * T-DM1 will be given at a predetermine dose
Receives: Drug: T-DM1; Drug: Pembrolizumab

What is being measured

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

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    The number and type of DLTs as defined in the protocol that occur during the first 21 days of treatment and all maximum grade of all treatment-related adverse events using CTCAE v4.0 will be used to identify a safe and tolerable dose

    Measured: 21 days

Secondary outcomes (5)

  1. Objective Response Rate

    Objective Response Rate (ORR) is defined as the percentage of patients with complete or partial response evaluated by RECIST 1.1. Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: 2 years

  2. Progression Free Survival

    Progression Free Survival, estimated via Kaplan-Meier method, is defined as the time from study registration to radiographic evidence of disease progression or death due to any cause, whichever occurred first. Progression is measured using RECIST 1.1 criteria, defined as at least a 20% increase in size in target lesion and/or unequivocal progression of non-target lesions and/or appearance of new lesions. Patients alive without disease progression are censored at the date of last disease evaluation.

    Measured: 2 years

  3. Duration Of Response

    The duration of response, estimated via Kaplan-Meier method, is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause. Participants without events reported are censored at the last disease evaluation).

    Measured: 2 years

  4. Disease Control Rate

    Disease Control Rate will be determined by looking at the number of subjects who have either a complete response, partial response, or stable disease for greater than or equal to 18 weeks, per RECIST 1.1

    Measured: 18 weeks

  5. Overall Survival Rate

    OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

    Measured: 5 years

Timeline

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

  1. First posted26 Jan 2017 (estimated)
  2. Study start17 Feb 2017
  3. Primary completion29 Oct 2020
  4. Study completion5 Dec 2024

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03032107
Sponsor's protocol ID
16-492
Status last verified
Jan 2025
First submitted
23 Jan 2017
Last updated
27 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Waks AG, Keenan TE, Li T, Tayob N, Wulf GM, Richardson ET 3rd, Attaya V, Anderson L, Mittendorf EA, Overmoyer B, Winer EP, Krop IE, Agudo J, Van Allen EM, Tolaney SM. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. J Immunother Cancer. 2022 Oct;10(10):e005119. doi: 10.1136/jitc-2022-005119.

    PubMed 36252998

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing T-DM1 and Pembrolizumab in people with Breast Cancer, run by Dana-Farber Cancer Institute at 2 sites 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 34 inclusion and 16 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: finished, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 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.

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 2024). 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?

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: 21 days). 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 NCT03032107, which also lists 1 linked publication.

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 27 Jan 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in