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Carcinoma, Intraductal, NoninfiltratingEarly Phase 1NCT02872025

Immunotherapy in High-risk Ductal Carcinoma in Situ (DCIS)

A Early Phase 1 study testing Pembrolizumab and Intralesional mRNA 2752 in people with Carcinoma, Intraductal, Noninfiltrating, run by Laura Esserman at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a study to investigate the change in the immune microenvironment of high risk ductal carcinoma in situ (DCIS) after short term exposure to immunotherapy. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Carcinoma, Intraductal, Noninfiltrating
What is being tested?
Pembrolizumab and Intralesional mRNA 2752
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
12 Dec 2016to 31 Mar 2026
Phase
Early Phase 1
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Plan on having surgical treatment to remove the lesion
  • Have at least 2 of the following high-risk features associated with DCIS - high-grade (grade II-III), palpable mass, hormone receptor negative (less than 1%), Her2 positive, young age (less than 45 years old), and large size (greater than 5 cm) and abundant T cell infiltration.
  • Participants with extensive DCIS and a small component of invasive disease are eligible as long as the extent of invasive disease is 10% or less of the total burden of disease.
  • Participants with a history of tamoxifen and/or aromatase inhibitor use for treatment or prevention are eligible but should discontinue these medications at least 2 weeks prior to starting this trial
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be >=18 years of age on day of signing informed consent.
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  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Demonstrate adequate organ function (all screening labs should be performed within 3 months of treatment initiation):
  • Absolute Neutrophil Count (ANC) >=1,500/microliter (mcL).
  • Platelets >=100,000/mcL.
  • Hemoglobin >=9 g/dL or >=5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment).
  • Serum creatinine <=1.5 X upper limit of normal (ULN) OR
  • Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) >=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN.
  • Serum total bilirubin <=1.5 x ULN OR
  • Direct bilirubin <= ULN for subjects with total bilirubin levels > 1.5 ULN.
  • Aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) / serum glutamic-pyruvic transaminase (SGPT) <= 2.5 X ULN.
  • Albumin >=2.5mg/dL.
  • International Normalized Ratio (INR) or Prothrombin Time (PT) <=1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Activated Partial Thromboplastin Time (aPTT) <=1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • A female participants is eligible to participate if not pregnant, not breast feeding, and at least one of the following applies:
  • Not a person of childbearing potential (WOCBP) OR
  • A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 90 days .corresponding to time needed to eliminate any study treatment plus 30 days (a menstruation cycle) after the last dose of study treatment.
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • A male participant must agree to use a contraception during the treatment period and for at least 90 days corresponding to time needed to eliminate any study treatment plus an additional 120 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.

Who cannot join

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of 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 hormone positive DCIS (HR+) that is not Her2+.
  • Has invasive breast cancer. This does not include DCIS with <10% invasive component and a clinically node negative disease.
  • Has a known history of active Bacillus Tuberculosis (TB)
  • Hypersensitivity to mRNA-2752 for mRNA-2752 monotherapy and combination therapy and hypersensitivity to immune check point inhibitor for the combination therapy or any of its excipients.
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  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has active autoimmune disease that has required systemic treatment in the 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, etc.) is not considered a form of systemic treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen (HBsAg) reactive) or known active Hepatitis C virus (HCV) (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.
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Testing the Ability of Immunotherapy to Alter the Tumor Immune MicroEnvionment (TIME) and Reduce or Eradicate High Risk DCIS

This is a study to investigate the change in the immune microenvironment of high risk ductal carcinoma in situ (DCIS) after short term exposure to immunotherapy.

Read the detailed description

PRIMARY OBJECTIVES:

DOSE ESCALATION (Monotherapy Messenger RNA-2725 (mRNA-2752):

  1. To determine the efficacy of intralesional mRNA-2752 monotherapy in participants with ductal carcinoma in situ (DCIS) of the breast as measured by the change in the MRI tumor size/volume/enhancement. Absence of tumor on biopsy and increase in immune infiltrates as measured by immune multiplex assays.

II. To characterize the safety of mRNA-2752 and feasibility of intralesional administration of mRNA-2752 in patients with high-risk DCIS.

DOSE EXPANSION (mRNA-2752 with or without an immune checkpoint inhibitor):

  1. To determine the Magnetic resonance imaging (MRI) response rate and complete pathologic response rate with either mRNA-2752 monotherapy or combined therapy in high risk DCIS.

ENROLLMENT IN THE PREVIOUS COHORTS HAS BEEN COMPLETED.

Being tested
Pembrolizumab, Intralesional mRNA 2752
Medical subject headings
Carcinoma, Intraductal, Noninfiltrating

What participants receive

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

  • PembrolizumabDrug

    Also called Keytruda, MK-3475

    Injected intralesionally

  • Intralesional mRNA 2752Biological

    Also called mRNA 2752

    Injected intralesionally

Study groups in NCT02872025
Study groupRoleWhat they receive
CLOSED:Pembrolizumab intralesionally (IL) x 2 doses (Escalation Phase)ExperimentalParticipants, upon diagnosis with high risk DCIS, will be offered 2 doses of pembrolizumab injected intralesionally (IL) 3 weeks apart (+/- 1 week) with surgery 3 weeks (+/- 2 weeks) after the 2nd dose. The participant will then undergo the surgical treatment as determined by the surgeon and the participant (partial mastectomy or mastectomy).
Receives: Drug: Pembrolizumab
CLOSED:Pembrolizumab IL x 4 doses (Expansion Phase)ExperimentalParticipants, upon diagnosis with high risk DCIS, will be offered 4 doses of pembrolizumab injected intralesionally (IL) 3 weeks apart (+/- 1 week) with surgery 3 weeks (+/- 2 weeks) after the 4th dose. The participant will then undergo the surgical treatment as determined by the surgeon and the participant (partial mastectomy or mastectomy).
Receives: Drug: Pembrolizumab
CLOSED:Pembrolizumab IL x 2 doses + mRNA 2752 IL x 2-4 doses (Expansion Phase)ExperimentalParticipants, upon diagnosis with high risk DCIS, will be offered 2 doses of pembrolizumab and intralesional mRNA 2752 injected intralesionally (IL) 3 weeks apart (+/- 1 week) with surgery 3 weeks (+/- 2 weeks) after the 2nd dose. The participant will then undergo the surgical treatment as determined by the surgeon and the participant (partial mastectomy or mastectomy).
Receives: Drug: Pembrolizumab; Biological: Intralesional mRNA 2752
mRNA-2752 Monotherapy x 2-4 doses (Escalation Cohort)ExperimentalParticipants will be offered up to 4 doses of mRNA-2752 injected intralesionally (IL) 3 weeks apart (+/- 1) week) with surgery or core biopsy 3 weeks (+/-1 week). The participants will proceed to biopsy, either image guided or excisional or partial mastectomy
Receives: Biological: Intralesional mRNA 2752
mRNA-2752 x 2-4 doses with or without immune checkpoint inhibitor (Expansion Cohort)ExperimentalParticipants will be will be offered injections of mRNA-2752 given on up to 4 occasions, 3 weeks apart (+/- 1 week) or a combination mRNA-2752 and immune checkpoint inhibitor will be given up to 4 occasions, 3 weeks apart (+/- 1 week). The participants will proceed to biopsy, either image guided or excisional or partial mastectomy.
Receives: Biological: Intralesional mRNA 2752
No active treatmentNo interventionThe control group will proceed to surgery alone within a 4 month timeframe following the diagnosis of high risk DCIS.

What is being measured

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

  1. Maximum tolerated dose (MTD)

    To determine the maximum tolerated dose (MTD), and recommended dose for subsequent expansion cohort, of intralesionally administered pembrolizumab in patients with ductal carcinoma in situ (DCIS) of the breast.

    Measured: 18 months

  2. Number of participants with Dose-limiting toxicities (DLTs)

    To define the dose-limiting toxicities (DLTs), tolerability, and feasibility of intralesional administration of pembrolizumab in patients with DCIS.

    Measured: 18 months

  3. Percentage of patients who demonstrate an increase (baseline vs. post intralesional injection) in intralesional CD8+ T cells

    To determine the response rate to intralesional pembrolizumab in patients with DCIS, as measured by an increase (baseline vs. post treatment) in intralesional CD8+ T cells, compared to untreated controls.

    Measured: post intralesional injection

Timeline

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

  1. First posted18 Aug 2016 (estimated)
  2. Study start12 Dec 2016
  3. Primary completion31 Mar 2026 (estimated)
  4. Study completion31 Mar 2026 (estimated)

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
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02872025
Sponsor's protocol ID
16704
Other IDs
NCI-2017-01320
Status last verified
Jan 2025
First submitted
10 Aug 2016
Last updated
30 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ramalingam K, Woody R, Glencer A, Schwartz CJ, Mori H, Wong J, Hirst G, Rosenbluth J, Onishi N, Gibbs J, Hylton N, Borowsky AD, Campbell M, Esserman LJ. Intratumoral Injection of mRNA-2752 and Pembrolizumab for High-Risk Ductal Carcinoma In Situ: A Phase 1 Nonrandomized Clinical Trial. JAMA Oncol. 2025 Mar 1;11(3):288-292. doi: 10.1001/jamaoncol.2024.5927.

    PubMed 39821301

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Pembrolizumab and Intralesional mRNA 2752 in people with Carcinoma, Intraductal, Noninfiltrating, run by Laura Esserman 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 24 inclusion and 15 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 30 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 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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?

Maximum tolerated dose (MTD) (time frame: 18 months). The study lists 3 primary outcomes in all. 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 NCT02872025, 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 30 Jan 2025.

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