Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Carcinoma, Ductal

Carcinoma in Situ

Carcinoma, Intraductal, Noninfiltrating

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Breast Neoplasms

Breast Carcinoma In Situ

Antineoplastic Agents

All Drugs and Chemicals

Immune Checkpoint Inhibitors

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Participants, 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).

Participants, 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).

Participants, 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).

Participants 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

Participants 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.

The control group will proceed to surgery alone within a 4 month timeframe following the diagnosis of high risk DCIS.

Intralesional mRNA 2752

Laura Esserman, MD

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.

PRIMARY OBJECTIVES:

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

* 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.
* 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):

\*To determine the 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.

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

To determine whether intralesional pembrolizumab with or without mRNA 2752 decreases tumor volume on MRI imaging

To characterize changes in the immune landscape of DCIS following intralesional administration of pembrolizumab with or without mRNA 2752.

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.

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

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immunotherapy in High-risk Ductal Carcinoma in Situ (DCIS)	NCT02872025	Carcinoma, Intr...	Pembrolizumab Intralesional m...	18 Years -	University of California, San Francisco
Immunotherapy in High-risk Ductal Carcinoma in Situ (DCIS)	NCT02872025	Carcinoma, Intr...	Pembrolizumab Intralesional m...	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for intralesional mrna 2752