Study Stopped
enrollment
Ipilimumab, Nivolumab, and Talimogene Laherparepvec Before Surgery in Treating Participants With Localized, Triple-Negative or Estrogen Receptor Positive, HER2 Negative Breast Cancer-deleted
A Phase 1 Study of Ipilumumab, Nivolumab and Talimogene Laherparepvec Preoperative Treatment of Localized Breast Cancer-deleted
3 other identifiers
interventional
6
1 country
1
Brief Summary
This phase I trial studies talimogene laherparepvec given together with ipilimumab and nivolumab before surgery in patients with triple-negative or estrogen receptor positive, HER2 negative localized breast cancer. Ipilimumab and Nivolumab are immune checkpoint inhibitors that enhance immune response towards cancer cells. Talimogene laherparepvec is a modifies human herpes virus 1 that is an oncolytic virus targeting cancer cells and makes tumor microenvironment more immunogenic to promote immune response against cancer. This study will assess the safety and efficacy of talimogene laherparepvec, ipilimumab, and nivolumab, and provide an insight for further improvement of immunotherapy in breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2019
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 3, 2019
CompletedStudy Start
First participant enrolled
July 10, 2019
CompletedFirst Posted
Study publicly available on registry
December 4, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 17, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 17, 2023
CompletedAugust 15, 2023
August 1, 2023
3.9 years
July 3, 2019
August 11, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence and severity of adverse events (AEs)
Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 toxicity criteria. AEs will be tabulated by type, severity, and the proportion of subject experiencing the event.
Up to 100 days after last study drug
Secondary Outcomes (1)
histopathological evaluation of changes of tumor for inflammatory infiltration and tumor necrosis
Up to 2 years
Study Arms (1)
Treatment (talimogene laherparepvec, nivolumab, ipilimumab)
EXPERIMENTALParticipants receive talimogene laherparepvec intratumorally on days 1, 22, and 36, nivolumab IV over 60 minutes on days 1, 15, 29, and 43, and ipilimumab IV over 90 minutes on days 1 and 43 in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given intratumorally
Eligibility Criteria
You may qualify if:
- Written informed consent must be obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- Localized, palpable, biopsy proven triple negative or ER positive HER2 negative infiltrating ductal breast cancer with size \> 1.5 cm by palpation, excluding breast cancer where neoadjuvant chemotherapy is indicated by current guidelines (i.e. inflammatory subtype, etc.)
- Tumor that is palpable and injectable
- Hemoglobin \>= 9 g/dL
- Absolute neutrophil count \>= 1,500/mm\^3
- Platelet count \>= 100,000/mm\^3
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal (ULN)
- Bilirubin =\< 1.5 x ULN; for subjects with documented/suspected Gilbert?s disease, bilirubin =\< 3 x ULN
- Albumin \>= 2.5 g/dl
- Prothrombin time (PT) / International normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 x institutional upper limit of normal unless the patient is on anticoagulant therapy within 28 days prior to enrollment (if the patient is receiving anticoagulant therapy, PT, and a PTT must be within therapeutic range of intended use of anticoagulants)
- Patients must be willing to submit blood and tissue specimens for translational medicine studies
- Patients must be offered the opportunity to participate in specimen banking for future research
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of study drug
- Women must not be breastfeeding
- +2 more criteria
You may not qualify if:
- Contraindications to tumor biopsy and injections (coagulopathy, known history of keloid formation, etc.)
- Women who are pregnant or breastfeeding
- Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec
- Inability to give informed consent
- History of malignancies except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix; for other malignancies, must be documented to be free of cancer for \>= 2 years. All other cases can be considered on a case by case basis at the discretion of the principal investigator
- Any condition that might interfere with the subject?s participation in the study, safety, or in the evaluation of the study results
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody, or any anti-CTLA 4 antibodies
- Patients must not have received prior treatment with talimogene laherparepvec or other oncolytic virus agents
- Patients must not have received any live vaccine within 30 days prior to registration. Seasonal flu vaccines that do not contain live virus are permitted
- Patients must not have an active infection requiring systemic therapy nor a viral infection requiring intermittent treatment with an antiherpetic drug, other than intermittent topical use
- Patients must not have active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis) which requires intermittent or chronic treatment with an anti-herpetic drug other than intermittent topical use
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable
- Patient must not have evidence of any clinically significant immunosuppression such as the following: primary immunodeficiency state such as severe combined immunodeficiency disease; concurrent opportunistic infection; receiving systemic immunosuppressive therapy within 28 days before enrollment with the exceptions of intranasal, topical, and inhaled corticosteroids or oral corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
- Patients must not have known history human immunodeficiency virus (HIV)
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
Related Publications (1)
Nguyen VP, Campbell KM, Nowicki TS, Elumalai N, Medina E, Baselga-Carretero I, DiNome ML, Chang HR, Oseguera DK, Ribas A, Glaspy JA. A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-negative Breast Cancer. Cancer Res Commun. 2023 Aug 23;3(8):1628-1637. doi: 10.1158/2767-9764.CRC-23-0145. eCollection 2023 Aug.
PMID: 37621406DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
John A Glaspy
UCLA / Jonsson Comprehensive Cancer Center
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
July 3, 2019
First Posted
December 4, 2019
Study Start
July 10, 2019
Primary Completion
May 17, 2023
Study Completion
May 17, 2023
Last Updated
August 15, 2023
Record last verified: 2023-08