Immunotherapy in High-risk Ductal Carcinoma in Situ (DCIS)
Testing the Ability of Immunotherapy to Alter the Tumor Immune MicroEnvionment (TIME) and Reduce or Eradicate High Risk DCIS
2 other identifiers
interventional
42
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for early_phase_1
Started Dec 2016
Longer than P75 for early_phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 10, 2016
CompletedFirst Posted
Study publicly available on registry
August 18, 2016
CompletedStudy Start
First participant enrolled
December 12, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2026
CompletedJanuary 30, 2025
January 1, 2025
9.3 years
August 10, 2016
January 29, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
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.
18 months
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.
18 months
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.
post intralesional injection
Other Outcomes (2)
Changes in Mean Tumor volume
18 months
Exploratory immunological responses to pembrolizumab before and after intralesional injection as measured using multiplex immunofluorescence on formalin-fixed paraffin-embedded (FFPE) tissue sections
18 months
Study Arms (6)
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).
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).
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).
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
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.
No active treatment
NO INTERVENTIONThe control group will proceed to surgery alone within a 4 month timeframe following the diagnosis of high risk DCIS.
Interventions
Injected intralesionally
Injected intralesionally
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- +9 more criteria
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Laura Essermanlead
- Merck Sharp & Dohme LLCcollaborator
- ModernaTX, Inc.collaborator
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
Related Publications (1)
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.
PMID: 39821301DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Laura Esserman, MD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
August 10, 2016
First Posted
August 18, 2016
Study Start
December 12, 2016
Primary Completion
March 31, 2026
Study Completion
March 31, 2026
Last Updated
January 30, 2025
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will not share