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

NCT05539365 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: I 1680021NCI-2022-07097
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Objective response rate

  Up to 2 years

Other Outcomes (2)

• Health-related quality of life (HR-QOL)

  Up to day 85

• Quality of Life as measured by the Perceived Stress Scale

  Up to day 85

Study Arms (1)

Treatment (ST-alpha-DC1, pembrolizumab)

EXPERIMENTAL

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.

Biological: Alpha-type-1 Polarized Dendritic Cells; Procedure: Biopsy; Procedure: Computed Tomography; Procedure: Leukapheresis; Biological: Pembrolizumab; Other: Quality-of-Life Assessment

Interventions

Alpha-type-1 Polarized Dendritic Cells BIOLOGICAL

Given IT

Also known as: alphaDC1

Treatment (ST-alpha-DC1, pembrolizumab)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (ST-alpha-DC1, pembrolizumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (ST-alpha-DC1, pembrolizumab)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (ST-alpha-DC1, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (ST-alpha-DC1, pembrolizumab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (ST-alpha-DC1, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Biopsy; Leukapheresis; pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation

Study Officials

• Shipra Gandhi

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2022
• First Posted: September 14, 2022
• Study Start: February 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: January 29, 2025

Record last verified: 2025-01

Locations

US (1)