| Eligibility |
Inclusion Criteria:
1. Women or men 18 years or older with metastatic or locoregionally recurrent
HER2-negative breast cancer. Resectable disease allowed.
2. 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.
3. Histologic or cytologic confirmation of invasive breast cancer that is HER2-negative
by standard clinical criteria.
4. Patients who will participate in the endocrine therapy cohort must have invasive
breast cancer that is ER+ (>=1% ER staining by IHC).
5. 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).
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
7. Concomitant use of bisphosphonates, RANKL antibody, and ovarian suppression is
allowed.
8. 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
9. Females of child-bearing potential (FCBP) should have a negative urine or serum
pregnancy test within 72 hours prior to enrollment. If urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required. FCBP must
also be willing to adhere to acceptable forms of birth control (a physician-approved
contraceptive method: tubal ligation; intra-uterine device; barrier contraceptive with
spermicide; or vasectomized partner) during the study treatment and through 3 months
after the last dose of talimogene laherparepvec.
FCBP are defined as sexually mature women who:
- Have not undergone a hysterectomy (the surgical removal of the uterus) or bilateral
oophorectomy (the surgical removal of both ovaries) or,
- Have not been naturally postmenopausal for at least 12 consecutive months (i.e. has
had menses at any time during the preceding 12 consecutive months)
- Must be willing to practice abstinence or use effective contraception for a minimum of
3 months following completion of study treatment (in addition to during study
therapy).
Exclusion Criteria:
1. Any significant medical condition, laboratory abnormalities, which places the subject
at unacceptable risk if he/she were to participate in the study.
2. Any condition that confounds the ability to interpret data from the study.
3. 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).
4. 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.
5. Patients with leptomeningeal disease.
6. 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.
7. 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.
8. Nab-paclitaxel arm: Grade 2 or higher neuropathy.
9. Known history of: cardiac disease, heart failure or decreased left ventricular
ejection fraction, significant clinical arrhythmias.
10. Patients must not have received an investigational agent within 4 weeks or <= 5
half-lives, whichever is shorter, prior to starting study treatment.
11. 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.
12. Major surgery or radiation = 2 weeks prior to starting study treatment or who have not
recovered from side effects of surgery or radiation.
13. Active herpetic skin lesions or prior complications of HSV-1 infection (e.g. herpetic
encephalitis or keratitis).
14. Lesions with underlying infection or clinically meaningful bleeding.
15. 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.
16. Previous treatment with talimogene laherparepvec or any other oncolytic virus.
17. Prior therapy with tumor vaccine.
18. Received live vaccine within 28 days prior to enrollment.
19. Known allergic reaction to talimogene laherparepvec, nab-paclitaxel, gemcitabine,
carboplatin, aromatase inhibitors, tamoxifen, fulvestrant, or any of their components.
An exception is made if the patient will not be receiving the offending
agent/component (i.e. a patient who is allergic to nab-paclitaxel but will be
receiving endocrine therapy is eligible).
20. Patients on therapeutic anticoagulation that cannot be held around injections.
21. Women who are pregnant or breast-feeding.
22. FCBP who are unwilling to use acceptable method(s) of effective contraception during
study treatment and through 3 months after the last dose of talimogene laherparepvec.
23. Sexually active subjects and their partners unwilling to use a 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.
24. Subjects who are unwilling to minimize exposure with his/her blood or other body
fluids to individuals who are at higher risks for HSV 1 induced complications
(immunosuppressed individuals, HIV positive individuals, pregnant women, or children
under the age of 1 year) during talimogene laherparepvec treatment and through 30 days
after the last dose of talimogene laherparepvec.
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