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About
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.
Full description
PRIMARY OBJECTIVES:
I. To explore the safety of talimogene laherparepvec in combination with nivolumab and ipilimumab in this population assessed by the frequency and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 toxicity criteria.
SECONDARY OBJECTIVES:
I. Assess tumor response of talimogene laherparepvec in combination with nivolumab and ipilimumab comparing to no treatment, in subjects with localized estrogen receptor (ER) positive and triple negative infiltrating ductal breast cancer.
II. Descriptively analyze the evidence of tumor necrosis and inflammatory infiltration on histopathological examination and immuno-oncological findings in tumor and peripheral blood of patients treated with talimogene laherparepvec in combination with nivolumab and ipilimumab.
EXPLORATORY OBJECTIVES:
I. Descriptively compare tumor response in patients whose tumors are PD-L1 positive (+) and PD-L1 negative (-) at baseline.
II. Determine the baseline mutational load of patients at the start of treatment and relate it to the response to treatment.
III. Determine if hormone receptor status correlates with tumor responses. IV. Determine the number of tumor infiltrating lymphocytes in patient samples at the start and at the end of treatment and relate them to tumor response.
V. Analyze T-cell receptor (TCR) repertoire in tumor infiltrating lymphocytes and peripheral blood mononuclear cells.
OUTLINE:
Participants receive talimogene laherparepvec intratumorally on days 1, 22, and 36, nivolumab intravenously (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.
After completion of study treatment, participants are followed up for 30 days.
Enrollment
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Inclusion criteria
Exclusion criteria
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)
Clinical or laboratory evidence of an active herpetic infection and in patients who require daily antiviral therapy such as acyclovir
Active or prior documented autoimmune disease within the past 3 years
Active or prior documented inflammatory bowel disease
History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids or has current ILD/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
Exposure to any investigational drug within 7 days prior to screening visit or for which 5 half-lives have not elapsed
Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
Primary purpose
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Interventional model
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6 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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