T-VEC With Chemotherapy or Endocrine Therapy in Treating Participants With HER2- Negative Breast Cancer

NCT03554044 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 17753NCI-2018-00652
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trials studies the side effects and how well talimogene laherparepvec works when given together with chemotherapy or endocrine therapy in treating patients with breast cancer that does not express the human epidermal growth factor receptor 2 (HER2) protein and has spread to other places in the body (metastatic), cannot be removed by surgery (unresectable), or has come back (recurrent). Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may attack specific tumor cells and stop them from growing or kill them. Chemotherapy drugs, such as nab-paclitaxel, gemcitabine, and 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. Estrogen can cause the growth of breast cancer cells. Drugs used as endocrine therapy, such as letrozole, anastrozole, exemestane, tamoxifen or fulvestrant, may lessen the amount of estrogen made by the body or may may stop the growth of tumor cells by blocking estrogen from connecting to the cancer cells. Giving talimogene laherparepvec with chemotherapy or endocrine therapy may work better in treating patients with HER2-negative breast cancer.

Conditions

Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Estrogen Receptor Positive; HER2/Neu Negative; Invasive Breast Carcinoma; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Recurrent Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of patients with treatment-related toxicities by maximum observed grade

  Treatment-related toxicities will be assessed according to NCI CTCAE v4.03, for all patients who receive at least one dose of study treatment. The distribution for the maximum observed grade for each adverse event will be tabulated and reported with 95% confidence interval

  Up to 2.5 years

• Maximum tolerated volume

  The maximum tolerated volume will be the highest volume (up to 4mL) that results in \<=1 dose limiting toxicity (DLT) in 6 treated patients for the chemotherapy group. At least 15 patients will be treated in the chemotherapy cohort and at least 6 patients will be treated in the endocrine therapy cohort.

  Up to 2.5 years

Secondary Outcomes (2)

• Overall response rate (ORR)

  Up to 2.5 years

• Response duration

  Up to 2.5 years

Study Arms (2)

Cohort I (talimogene laherparepvec, chemotherapy)

EXPERIMENTAL

Patients receive talimogene laherparepvec intra-tumorally (IT) every 2 weeks for the first 10 weeks and every 3 weeks thereafter along with one of the following chemotherapies: paclitaxel (IV), nab-paclitaxel IV, or gemcitabine / carboplatin IV. Cycles repeat every 21 days until disease progression or unacceptable toxicity

Drug: Paclitaxel; Biological: Talimogene Laherparepvec; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Carboplatin

Cohort II (talimogene laherparepvec, endocrine therapy)

EXPERIMENTAL

Patients receive talimogene laherparepvec intra-tumorally (IT) every 2 weeks for the first 10 weeks and every 3 weeks thereafter along with letrozole PO, anastrazole PO, exemestane PO, tamoxifen PO on days 1-21 or fulvestrant IM every 2 weeks for 3 doses then every 4 weeks for the subsequent courses. Cycles repeat every 28 days until disease progression or unacceptable toxicity

Drug: Anastrozole; Drug: Exemestane; Drug: Fulvestrant; Drug: Letrozole; Biological: Talimogene Laherparepvec; Drug: Tamoxifen

Interventions

Anastrozole DRUG

Given PO

Also known as: Arimidex, ICI-D1033, ZD-1033

Cohort II (talimogene laherparepvec, endocrine therapy)

Exemestane DRUG

Given PO

Also known as: Aromasin, FCE-24304

Cohort II (talimogene laherparepvec, endocrine therapy)

Fulvestrant DRUG

Given IM

Also known as: Faslodex, ICI 182,780, ZD9238

Cohort II (talimogene laherparepvec, endocrine therapy)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Cohort II (talimogene laherparepvec, endocrine therapy)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Cohort I (talimogene laherparepvec, chemotherapy)

Talimogene Laherparepvec BIOLOGICAL

Given IT

Also known as: 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, OncoVEXGM-CSF

Cohort I (talimogene laherparepvec, chemotherapy); Cohort II (talimogene laherparepvec, endocrine therapy)

Tamoxifen DRUG

Given PO

Also known as: Nolvadex

Cohort II (talimogene laherparepvec, endocrine therapy)

Nab paclitaxel DRUG

Given IV

Also known as: Abraxane

Cohort I (talimogene laherparepvec, chemotherapy)

Gemcitabine DRUG

Given IV

Also known as: Gemzar

Cohort I (talimogene laherparepvec, chemotherapy)

Carboplatin DRUG

Given IV

Also known as: Paraplatin

Cohort I (talimogene laherparepvec, chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Women or men 18 years or older with metastatic or locoregionally recurrent HER2-negative breast cancer. Resectable disease allowed.
• Ability to understand and voluntarily sign informed consent prior to undergoing any study-related assessments or procedures, as well as adhere to the study visit schedule and other protocol requirements.
• Histologic or cytologic confirmation of invasive breast cancer that is HER2-negative by standard clinical criteria.
• Patients who will participate in the endocrine therapy cohort must have invasive breast cancer that is ER+ (\>=1% ER staining by IHC).
• At least one accessible and injectable lesion (ie. breast, chest wall, skin nodule or mass, axillary or supraclavicular lymph node) of at least 1cm. (Ultrasound imaging may be used as clinically indicated. Injection must be able to be performed at the bedside).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Concomitant use of bisphosphonates, RANKL antibody, and ovarian suppression is allowed.
• Adequate organ function:
• Absolute neutrophil count (ANC) \>= 1.5x109/L for chemotherapy cohort, and \>= 1.0x109/L for endocrine therapy cohort
• Hemoglobin (Hgb) \>= 9g/dL
• Platelets (plt) \>= 100 x 109/L for chemotherapy cohort, and \>=75, 000 for endocrine therapy cohort
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=2.5 x Upper Limit Normal (ULN). If liver metastases present \<=5 x ULN allowed.
• Serum total bilirubin \<= 1.5 x ULN or direct bilirubin \<= 1.5 × ULN in patients with well documented Gilbert's Syndrome
• Serum creatinine \<= 1.5 x ULN, or 24-hr clearance \>= 60ml/min
• International normalization ratio (INR) or prothrombin time (PT) or partial thromboplastin time (PTT)/ activated partial thromboplastin time (aPTT) \<= 1.5 x ULN

You may not qualify if:

• Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Any condition that confounds the ability to interpret data from the study.
• Patients must have recovered from side effects resulting from prior cancer-directed therapy to a level of grade 1 or less (unless deemed not clinically significant by study investigator).
• Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 4 weeks after whole-brain radiotherapy (WBXRT) or 2 weeks after Stereotactic radiosurgery (SRS) are allowed. Patients must be stable off steroids for brain metastases for at least 7 days. Subjects with asymptomatic clinically insignificant brain metastases not requiring treatment are allowed. The exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Patients with leptomeningeal disease.
• History of symptomatic autoimmune disease or active autoimmune disease that has required systemic treatment in the 2 weeks prior to enrollment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Evidence of immune suppression due to: a) known human immunodeficiency virus (HIV) infection or AIDS; b) known leukemia or lymphoma; c) those who require high dose steroids (\>10 mg/day of prednisone or equivalent within 7 days prior to enrollment) or other immunosuppressive therapies (\>2weeks); d) active hepatitis B or C; e) congenital or acquired cellular and/or humoral immune deficiency; f) other signs or symptoms of immune system suppression or concurrent opportunistic infection.
• Nab-paclitaxel arm: Grade 2 or higher neuropathy.
• Known history of: cardiac disease, heart failure or decreased left ventricular ejection fraction, significant clinical arrhythmias.
• Patients must not have received an investigational agent within 4 weeks or \<= 5 half-lives, whichever is shorter, prior to starting study treatment.
• Last dose of prior chemotherapy must be at least 2 weeks, and 2 weeks for targeted therapies, before first dose of study treatment. There is no required washout for endocrine therapy.
• Major surgery or radiation ≤ 2 weeks prior to starting study treatment or who have not recovered from side effects of surgery or radiation.
• Active herpetic skin lesions or prior complications of HSV-1 infection (e.g. herpetic encephalitis or keratitis).
• Lesions with underlying infection or clinically meaningful bleeding.
• Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g. acyclovir), other than intermittent topical use. Patients requiring anti-herpetic prophylaxis during chemotherapy are excluded.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Amgen: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Huppert LA, Gliwa AS, Tait M, Quintal L, Starzinski S, Cheung A, Moasser M, Majure M, Melisko M, Munster P, Rugo HS, Campbell M, Fong L, Chien AJ. Phase Ib study of intratumoral talimogene laherparepvec (T-VEC) in combination with chemotherapy or endocrine therapy in patients with advanced HER2-negative breast cancer. NPJ Breast Cancer. 2025 Nov 21;11(1):130. doi: 10.1038/s41523-025-00842-8.

  PMID: 41271741 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; exemestane; Fulvestrant; Letrozole; Paclitaxel; Taxes; talimogene laherparepvec; Tamoxifen; Albumin-Bound Paclitaxel; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Coordination Complexes

Study Officials

• Amy J Chien, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor

Study Record Dates

• First Submitted: May 30, 2018
• First Posted: June 12, 2018
• Study Start: February 5, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: May 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)