Immunotherapy for Intraductal Carcinoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Female
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Waitlist Available
Sponsor: Laura Esserman
No Placebo Group
Breakthrough Therapy
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?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.
What safety data is available for the immunotherapy treatment involving Pembrolizumab and related therapies?
Pembrolizumab (Keytruda) is associated with immune-related adverse events (irAEs), including type 1 diabetes mellitus in 0.2% of cases, pneumonitis in 1%-5% of patients, and other immune-mediated reactions like colitis, hepatitis, and thyroid disorders. Common adverse reactions include fatigue, cough, nausea, rash, and diarrhea. Despite these risks, the benefits in treating life-threatening diseases like metastatic melanoma and non-muscle invasive bladder cancer have been considered to outweigh the risks.
12369Is the drug Pembrolizumab a promising treatment for Intraductal Carcinoma?
Pembrolizumab is a promising drug because it helps the immune system fight cancer by targeting a specific pathway (PD-1/PD-L1) that tumors use to hide from immune cells. It has shown effectiveness in treating various cancers, like lung cancer and melanoma, and is approved for use in several types of tumors. Its ability to work in different cancers suggests it could be promising for Intraductal Carcinoma as well.
135710What data supports the idea that Immunotherapy for Intraductal Carcinoma is an effective treatment?
The available research does not provide specific data supporting the effectiveness of immunotherapy for Intraductal Carcinoma. Instead, it discusses the use of pembrolizumab, a drug used in immunotherapy, for other types of cancer. For example, pembrolizumab showed minimal benefit for most patients with pancreatic cancer, but there was a case where a patient with a specific type of pancreatic cancer had a prolonged response to the drug. Additionally, pembrolizumab was tested in lung and ovarian cancers, but the results focused on safety and tolerability rather than effectiveness. Therefore, there is no direct evidence from the provided research that supports the effectiveness of this treatment for Intraductal Carcinoma.
347810Do I need to stop taking my current medications for the trial?
If you are using tamoxifen or aromatase inhibitors, you must stop taking them at least 2 weeks before starting the trial. The protocol does not specify about other medications.
Eligibility Criteria
This trial is for adults with high-risk ductal carcinoma in situ (DCIS) who plan to have surgery, are not pregnant or breastfeeding, and agree to use contraception. Eligible participants must have certain high-risk features like a palpable mass or hormone receptor negative status, be in good physical condition (ECOG 0-1), and demonstrate adequate organ function.Inclusion Criteria
I am planning to have surgery to remove my cancer.
I am fully active or restricted in physically strenuous activity but can do light work.
I am using two birth control methods or am not able to have children, and will continue for 120 days after my last dose.
My kidney function is within the required range.
My breast cancer is aggressive, based on at least 2 high-risk features.
I am 18 years old or older.
My liver function tests are within the required range.
Exclusion Criteria
I am not allergic to mRNA-2752 or immune checkpoint inhibitors.
I have had or currently have lung inflammation treated with steroids.
My breast cancer is hormone-receptor positive but not HER2 positive.
I have been diagnosed with HIV.
I have an immune system disorder or have been on steroids or other immune-weakening medicines in the last week.
I have an active TB infection.
I haven't needed systemic treatment for an autoimmune disease in the last 2 years.
I have not received a live vaccine in the last 30 days.
Participant Groups
The study tests the effects of short-term immunotherapy on DCIS using Pembrolizumab and Intralesional mRNA 2752 before surgical removal. It aims to understand how these treatments alter the immune environment within the breast tissue affected by cancer.
6Treatment groups
Experimental Treatment
Active Control
Group I: mRNA-2752 x 2-4 doses with or without immune checkpoint inhibitor (Expansion Cohort)Experimental Treatment1 Intervention
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.
Group II: mRNA-2752 Monotherapy x 2-4 doses (Escalation Cohort)Experimental Treatment1 Intervention
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
Group III: CLOSED:Pembrolizumab intralesionally (IL) x 2 doses (Escalation Phase)Experimental Treatment1 Intervention
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).
Group IV: CLOSED:Pembrolizumab IL x 4 doses (Expansion Phase)Experimental Treatment1 Intervention
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).
Group V: CLOSED:Pembrolizumab IL x 2 doses + mRNA 2752 IL x 2-4 doses (Expansion Phase)Experimental Treatment2 Interventions
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).
Group VI: No active treatmentActive Control1 Intervention
The control group will proceed to surgery alone within a 4 month timeframe following the diagnosis of high risk DCIS.
Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:
🇺🇸 Approved in United States as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇪🇺 Approved in European Union as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇬🇧 Approved in United Kingdom as KEYTRUDA for:
- Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of California, San FranciscoSan Francisco, CA
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Who is running the clinical trial?
Laura EssermanLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
ModernaTX, Inc.Industry Sponsor
References
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.
Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]Pembrolizumab is a full-length human immunoglobulin G4 (IgG4) monoclonal antibody directed against the immune checkpoint PD-1 to remove its binding with PD-L1 and thus to restore an anti-tumor immune response of T cells. Pembrolizumab is one of the most advanced immune checkpoint inhibitors for cancer care. Apart from rare and serious adverse effects, its favorable tolerance profile enables to treat fragile patients who have often no other choice than best supportive care. The effective retained dose of pembrolizumab is a venous administration of 200 mg every 3 weeks until disease progression, intolerance or up to 24 months. Pembrolizumab has already proven its efficacy and thus obtained marketing authorization in so-called hot or hypermutated tumors or tumors expressing PD-L1 such as melanomas, non-small cell lung cancers, urothelial carcinomas, cervical cancer, etc. Pembrolizumab is also authorized in the United States in the treatment of mismatch repair-deficient tumors or with microsatellite instability. The current challenge is to expand its use in tumor types that are supposed to be less immunogenic, for example, by attempting to warm up the tumor microenvironment, or by combining pembrolizumab with other molecules. An acceptable toxicity profile of such combinations remains to explore. We review here the current indications of this drug, the main prognostic and predictive factors of its efficacy as well as the potential forthcoming indications.
FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
A Patient with Metastatic Microsatellite Instability-High Pancreatic Ductal Adenocarcinoma with a Prolonged Response to Single-Agent Pembrolizumab. [2021]Immunotherapy is an effective new approach in the treatment of many malignancies. However, pancreatic ductal adenocarcinoma (PDAC) does not usually respond to immunotherapy. We discuss the case of a patient with metastatic microsatellite instability-high PDAC who had a prolonged response to single-agent pembrolizumab for almost 3 years.
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]Pembrolizumab (Keytruda) is a monoclonal antibody against the programmed cell death-1 (PD-1) receptor on lymphocytes, which is one of the immune checkpoint inhibitors (ICIs) approved for multiple solid and hematologic malignancies. Although ICIs have proven to be more effective and less toxic compared to chemotherapy, there are reports of adverse side effects with ICIs. For example, pneumonitis is a potentially lethal side effect occurring in 1%-5% of patients who received ICIs in clinical trials, and there are case reports with clinical and radiological features of checkpoint inhibitor-pneumonitis (CIP).
Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. [2023]Pembrolizumab confers minimal benefit to most patients with pancreas cancer. We explored survival and patient treatment burden (for example, death within 14 days of therapy) in a subgroup who had early access to pembrolizumab .