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Anatomic Stage 0 Breast Cancer AJCC v8Phase 1NCT04185311

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 testing Ipilimumab, Nivolumab and Talimogene Laherparepvec in people with Anatomic Stage 0 Breast Cancer AJCC v8 and Anatomic Stage I Breast Cancer AJCC v8, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Ipilimumab, Nivolumab and Talimogene Laherparepvec
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
10 Jul 2019to 17 May 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Women of childbearing potential (WOCBP) must be willing to use either two adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy, or to abstain from heterosexual activity (complete abstinence) throughout the study, starting with visit 1 through 5 months after the last dose of study therapy. Approved contraceptive methods include, for example, intrauterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, female condoms with spermicide, or oral contraceptives. Spermicides alone are not an acceptable method of contraception. 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
  • Male patients must agree to use an adequate method of contraception, or to abstain from heterosexual activity (complete abstinence) starting with the first dose of study drug through 7 months after the last dose of study therapy

Who cannot join

  • 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
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  • 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
  • NOTE: Subjects with active, known or suspected autoimmune disease such as vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • 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
  • Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: A Phase 1 Study of Ipilumumab, Nivolumab and Talimogene Laherparepvec Preoperative Treatment of Localized Breast Cancer-deleted

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Ipilimumab, Nivolumab, Talimogene Laherparepvec
Medical subject headings
Breast Carcinoma In Situ, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4

    Given IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • Talimogene LaherparepvecBiological

    Also called ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene, Imlygic, JS1 34.5-hGMCSF 47- pA-, T-VEC

    Given intratumorally

Study groups in NCT04185311
Study groupRoleWhat they receive
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.
Receives: Biological: Ipilimumab; Biological: Nivolumab; Biological: Talimogene Laherparepvec

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 100 days after last study drug

Secondary outcomes (1)

  1. histopathological evaluation of changes of tumor for inflammatory infiltration and tumor necrosis

    Results will be reported using purely descriptive statistics. . All subjects that received any study therapy will be included in the analysis. This is a descriptive study, efficacy will be assessed by histological observations. No criteria for tumor response by its size, i.e. complete response (CR), partial response (PR), are used.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2019
  2. Study start10 Jul 2019
  3. Primary completion17 May 2023
  4. Study completion17 May 2023

Why it stopped: enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04185311
Sponsor's protocol ID
18-000427
Other IDs
NCI-2018-01410, Glaspy BMS CA209-9ET Breast
Status last verified
Aug 2023
First submitted
3 Jul 2019
Last updated
15 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37621406

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ipilimumab, Nivolumab and Talimogene Laherparepvec in people with Anatomic Stage 0 Breast Cancer AJCC v8 and Anatomic Stage I Breast Cancer AJCC v8, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: enrollment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (AEs) (time frame: Up to 100 days after last study drug). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04185311, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2023.

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