SGT-53, Carboplatin, and Pembrolizumab for the Treatment of Metastatic Triple Negative Inflammatory Breast Cancer

NCT05093387 | Withdrawn Phase 1 DMC FDA Drug

• 4 other identifiers: NU 19B07NCI-2021-09317STU00212682P30CA060553
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the effect of SGT-53, carboplatin, and pembrolizumab in treating patients with triple negative inflammatory breast that has spread to other parts of the body (metastatic). SGT-53 is a gene therapy that changes the deoxyribonucleic acid (DNA) of patients' tumor cells to make it easier for the immune system to recognize them. SGT-53 targets the TP53 gene, which is frequently mutated in IBC cells. Chemotherapy drugs, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving SGT-53, pembrolizumab, and carboplatin may help the control the disease in patients with triple negative inflammatory breast cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Breast Inflammatory Carcinoma; Metastatic Triple-Negative Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Rate of Successful Administration

  Assess feasibility of SGT-53 with carboplatin and pembrolizumab in metastatic triple negative IBC with a Combined Positive Score of ≥10 in PD-L1 expression.

  Up to 24 months

• Clinical Benefit Rate

  Evaluate preliminary activity of SGT-53 with carboplatin and pembrolizumab in metastatic triple negative IBC with a Combined Positive Score of ≥10 in PD-L1 expression, as measured by (complete response + particle response + stable disease \>= 6 months using Response Evaluation Criteria in Solid Tumors criteria version 1.1).

  Up to 3 cycles (each cycle = 21 days)

Secondary Outcomes (1)

• Incidence of adverse events

  Up to 28 (+/- 3 days) after last study treatment

Study Arms (1)

Interventional (SGT-53, pembrolizumab, carboplatin)

EXPERIMENTAL

Patients receive SGT-53 IV over 90-120 minutes on days 1, 8, and 15, pembrolizumab IV over 30 minutes on day 3, and carboplatin IV over 30-60 minutes on day 3. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Biological: Pembrolizumab; Genetic: Transferrin Receptor-Targeted Liposomal p53 cDNA

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Interventional (SGT-53, pembrolizumab, carboplatin)

Pembrolizumab BIOLOGICAL

Given IV

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

Interventional (SGT-53, pembrolizumab, carboplatin)

Transferrin Receptor-Targeted Liposomal p53 cDNA GENETIC

Given IV

Also known as: SGT-53, Synerlip p53

Interventional (SGT-53, pembrolizumab, carboplatin)

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically or cytologically confirmed diagnosis of breast cancer with a clinical diagnosis of IBC
• IBC diagnosis is based on the current or previous clinical evaluation demonstrating inflammatory changes in the involved breast. Pathological evidence of dermal lymphatic invasion should be noted but is not required for diagnosis. Diagnosis of IBC defined by:
• Rapid onset of breast erythema, edema and/or peau d'orange, and/or warm breast, with or without an underlying palpable mass
• Duration of history no more than six months
• Erythema occupying at least one-third of the breast
• Triple negative metastatic tumor, negative for hormone receptor and negative for HER2 as defined by the 2018 American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines
• Patients must have stage IV M1 measurable or evaluable disease as defined by RECIST v1.1, or non-measurable tumors
• Patient's tumors must express PD-L1 with a Combined Positive Score of \>= 10 as determined by the PD-L1 Immunohistochemistry (IHC) 22C3 pharmDx assay
• Patients must have progressed on \>= 1 prior systemic therapy for metastatic disease (prior therapies include standard neoadjuvant chemotherapy with anthracycline and taxane)
• Note: A 28 day wash out period for prior therapy before beginning study treatment is required
• Patients must be age \>= 18 years
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at registration
• Leukocytes \>= 2,000/mcL (within 14 days prior to registration)
• Absolute neutrophil count \>= 1,500/mcL (within 14 days prior to registration)
• Platelets \>= 100,000/mcl (within 14 days prior to registration)

You may not qualify if:

• Patients who have not recovered to =\< grade 1 from adverse events from chemotherapy, radiotherapy, surgery, or experimental therapies prior to entering the study are not eligible. Peripheral neuropathy must have recovered to =\< grade 2
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• Patients concurrently receiving any other investigational agents are not eligible
• Patients who have received prior radiotherapy within 14 days of registration are not eligible. 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-central nervous system (CNS) disease
• Patients who are currently participating in or have participated in a study of an investigational agent or have used an investigational device within 5 half-lives or 14 days (whichever is shorter) prior to the first dose of study treatment are not eligible
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been \>= 14 days after the last dose of the previous investigational agent
• Patients who have a history of allergic reactions or severe hypersensitivity attributed to compounds of similar chemical or biologic composition to pembrolizumab, carboplatin, or SGT-53 are not eligible
• Patients who have had prior exposure to compounds of similar chemical or biologic composition to pembrolizumab (antibodies to PD-1, PD-L1, PD-L2) or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137) in the metastatic setting are not eligible. Please contact the principle investigator for specific questions or interactions
• Patients with active autoimmune disease or history (within 2 years) of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), are not eligible. These include but are not limited to patients with a history of:
• Immune related neurologic disease
• Multiple sclerosis
• Autoimmune (demyelinating) neuropathy
• Guillain-Barre syndrome
• Myasthenia gravis
• Systemic autoimmune disease such as systemic lupus erythematosus (SLE)

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Carboplatin; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Massimo Cristofanilli, MD, FACP

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: October 26, 2021
• Study Start: November 10, 2022
• Primary Completion: November 10, 2022
• Study Completion: November 10, 2022
• Last Updated: November 15, 2022

Record last verified: 2022-11

Locations

US (1)