Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer

A Phase II Study of Intratumorally Injected Autologous Dendritic Cells (DCs) in PD-L1-Negative Treatment Naïve and in Refractory Metastatic Triple Negative Breast Cancer Patients

This phase II trial tests the safety, side effects, and whether dendritic cell-based treatment and pembrolizumab work in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). The term triple-negative breast cancer refers to the fact that the cancer cells don't have estrogen or progesterone receptors (ER or PR) and also don't make any or too much of the protein called HER2 (the cells test "negative" on all 3 tests). Dendritic cell-based treatment works by boosting the immune system (a system in our bodies that protects us against infection) to recognize and destroy the cancer cells. Pembrolizumab, is an immune checkpoint inhibitor drug, that works by targeting molecules that act as a check and balance system for immune responses. Immune checkpoint inhibitor drugs are designed to either "unleash" or "enhance" the cancer immune responses that already exist by either blocking inhibitory molecules or by activating stimulatory molecules. Giving dendritic cell-based therapy and pembrolizumab may decrease symptoms and improve quality of life in patients with triple negative breast cancer.

Study Overview

• Status: Withdrawn
• Conditions: Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma; Unresectable Triple-Negative Breast Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Biological: Pembrolizumab; Procedure: Leukapheresis; Procedure: Biopsy; Procedure: Computed Tomography; Biological: Alpha-type-1 Polarized Dendritic Cells

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the clinical efficacy and safety and tolerability of a combination of intratumorally injected autologous dendritic cells (DCs) and pembrolizumab in PD-L1 negative treatment-naive and refractory metastatic triple negative breast cancer patients.

SECONDARY OBJECTIVES:

I. To assess progression-free survival and overall survival in metastatic triple negative breast cancer patients that received the combination of intratumorally injected autologous DCs and pembrolizumab.

II. To assess the clinical efficacy in the non-injected target lesion (optional biopsies for this lesion).

OUTLINE:

Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 intratumorally (IT) on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab intravenously (IV) on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and computed tomography (CT) scans at baseline and days 50 and 85.

After completion of study treatment, patients are followed up at 30 and 90 days after the last dose of study drug, and then every 3 months for up to 2 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >= 18 years of age
• Pathologically confirmed diagnosis of unresectable or metastatic triple negative breast cancer (TNBC) with no curative treatment options
• At least 2 target lesions present per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at least one of which is amenable to biopsy and injection
• PD-L1 negative metastatic TNBC patients who are treatment naive in the first linen metastatic setting are eligible
• Both PD-L1 positive and PD-L1 negative metastatic TNBC patients in the second line setting and beyond are eligible
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2
• Platelets >= 75,000/uL
• Hemoglobin >= 8 g/dL
• Absolute Neutrophil Count (ANC) >= 1500/uL
• Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 30 mL/min for participant with creatinine levels >1.5 x institutional ULN
• Total bilirubin: =< 2 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 2 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT] =< 3 x institutional ULN (=< 5 x ULN for participants with liver metastases)
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Participants currently treated with systemic immunosuppressive agents, including steroids (> than equivalent of 10 mg daily of prednisone) are ineligible until 3 weeks after removal from immunosuppressive treatment
• Patients with active autoimmune disease or history of transplantation

• Cardiac risk factors including:

  • Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent
  • Patients with a New York Heart Association classification of III or IV
• Pregnant or nursing female participants
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=<2 weeks of radiotherapy) to non-CNS disease
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
• Has severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its excipients
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy

• Has active Human Immunodeficiency Virus (HIV) infection

  • Note: HIV testing is required

• Has active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection

  • Note: Testing for Hepatitis B and Hepatitis C is required
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit comp
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (ST-alpha-DC1, pembrolizumab); Patients undergo leukapheresis over 90 minutes. Patients then receive ST-alpha-DC1 IT on days 1, 8, and 50 in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on days 8, 29, 50, and 71 in the absence of disease progression or unacceptable toxicity. Patients who are receiving clinical benefit from treatment at the end of day 85, may continue to receive pembrolizumab IV every 3 weeks beyond the 4 study doses. Patients also undergo tumor biopsies on days 1, 8, and 50 and CT scans at baseline and days 50 and 85.

Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Biological: Pembrolizumab; Given IV; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475; Procedure: Leukapheresis; Undergo leukapheresis; Other Names: Leukocytopheresis; Therapeutic Leukopheresis; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Biological: Alpha-type-1 Polarized Dendritic Cells; Given IT; Other Names: alphaDC1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective responses rate (ORR)	Will be assessed by immune related response criteria (iRECIST).	Up to 2 years
Incidence of adverse events	Will be assessed using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and will be summarized by attribution and grade using frequencies and relative frequencies.	Up to 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Will be summarized using standard Kaplan-Meier methods, where the median times will be estimated with 90% confidence intervals.	Up to 2 years
Overall survival (OS)	Will be summarized using standard Kaplan-Meier methods, where the median times will be estimated with 90% confidence intervals.	Up to 2 years
Objective response rate	Objective response in the target lesion that is not injected will be summarized using frequencies and relative frequencies.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life (HR-QOL)	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) will be summarized by time point (pre- and post-treatment) using the appropriate descriptive statistics. The pre- and post-treatment levels will be compared using a permutation paired t-test.	Up to day 85
Quality of Life as measured by the Perceived Stress Scale	Measured using validated 10 question "Perceived Stress Scale" which assesses global stress (regardless of source). This 10 question survey uses a 0-4 scale with higher composite score corresponding to greater stress	Up to day 85

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Shipra Gandhi, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: September 9, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Breast Diseases; Carcinoma; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: I 1680021 (Other Identifier: Roswell Park Cancer Institute); NCI-2022-07097 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No