The purpose of this study is to find out more about talimogene laherparepvec (also known as
OncoVEXGM-CSF or IMLYGIC®) in people with a healthy immune system with confirmed low-risk
squamous cell carcinoma. Usually, low-risk SCC is treated with a surgical procedure, but
surgery can be challenging when patients have: multiple SCCs on their body, when the SCC is
on a challenging place on the body to remove or when patients are older or have diseases that
place them at risk for surgery related complications. Immune therapy is a treatment that uses
certain parts of a person's immune system to fight disease. Immune therapy is a proven
therapeutic approach in many cancers, including melanoma, another type of skin cancer.
Talimogene laherparepvec (TVEC) is made from a modified herpes simplex virus type 1 (HSV-1,
the "cold sore" virus). The virus' genes were modified in a laboratory so that it produces a
protein called human granulocyte macrophage colony-stimulating factor (GM-CSF), which
multiplies and grows in tumor cells. Human GM-CSF is normally produced by various cells
within the body and is used as a medicine to treat patients with white blood cell counts that
are too low. This modified HSV-1 produces a protein that acts on tumor cells and stimulates
the immune system. TVEC is administered by injection with a needle directly into one or more
tumors and works by directly destroying cancer cells and enhancing immune response to destroy
cancer cells.
Inclusion Criteria:
1. Able to give informed consent in English or Spanish
2. Age > 18
3. Have at least one >0.5 cm to <5.0 cm, histologically confirmed low risk cutaneous SCC
(including kerathoacanthomas)
- Size >0.5 cm on trunk or extremities (excluding face, neck feet, nail units, and
ankles)
- Clinically consistent with primary tumors.
- Lesion considered unresectable (as defined in Section 1.2)
- Recurrent lesions will be considered eligible if additional inclusion criteria
are met.
- No immunosuppression
- Not a site of previous radiation therapy or chronic significant inflammation
- Fast growing lesions (doubling in size over a 4 week period of time) will be
included if they are clinically suggestive of cSCC of the keratoacanthoma type.
- Well or moderately differentiated tumor as confirmed by skin biopsy
- Depth less than 2 mm (for non KA type cSCC )
- No perineural or vascular involvement in preliminary biopsy.
4. Partial biopsy of squamous cell skin cancer identified as a target lesion(s) to
determine the histological differentiation of the tumor or other adverse histological
features
5. In patients with multiple lesions, up to 3 lesions in a similar anatomical site,
(trunk, limbs etc) that is at least 10 cm apart can be selected.
6. Maximum of 5 lesions per patient can be selected for treatment
7. Adequate organ function determined within 28 days prior to enrollment, defined as
follows:
8. Hematology:
- Absolute neutrophil count ≥ 1500/mm3 (1.5x109/L)
- Platelet count ≥ 75,000/mm3 (7.5x109/L)
- Hemoglobin ≥ 8 g/dL (without need for hematopoietic growth factor or transfusion
support)
9. Renal
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN), OR 24-hour creatinine
clearance ≥ 60 mL/min for subject with creatinine levels > 1.5 x ULN. (Note:
Creatinine clearance need not be determined if the baseline serum creatinine is within
normal limits. Creatinine clearance should be determined per institutional standard)
10. Hepatic
- Serum bilirubin ≤ 1.5 x ULN
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN 23 | Page Version 6-26-2018
- Alanine aminotransferase (ALT) ≤ 2.5 x ULN
11. Coagulation
- International normalization ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN,
unless the subject is receiving anticoagulant therapy, in which case PT and
partial thromboplastin time (PTT)/ activated PTT (aPTT) must be within
therapeutic range of intended use of anticoagulants.
- PTT or aPTT ≤ 1.5 x ULN unless the subject is receiving anticoagulant therapy as
long as PT and PTT/aPTT is within therapeutic range of intended use of
anticoagulants.
12. Female subject of childbearing potential 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.
Exclusion Criteria:
1. Any patient with diagnosis of invasive cancer in the last 3 years with the exception
of stage I and II melanoma, cutaneous BCC and SCCs will be excluded.
2. Subjects on acitretin, capecitabine, topical chemotherapies or treatments.
3. History or evidence of symptomatic autoimmune disease (eg, pneumonitis,
glomerulonephritis, vasculitis, or other), or history of active autoimmune disease
that has required systemic treatment (ie, use of corticosteroids, immunosuppressive
drugs or biological agents used for treatment of autoimmune diseases) in past 2 months
prior to enrollment. Replacement therapy (eg, thyroxine for hypothyroidism, insulin
for diabetes or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency) is not considered a form of systemic treatment for autoimmune
disease.
4. Evidence of clinically significant immunosuppression such as the following:
- Primary immunodeficiency state such as Severe Combined Immuno deficiency Disease
- Acquired immunodeficiency syndrome
- Concurrent opportunistic infection
- Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid
doses > 10 mg/day of prednisone or equivalent within 2 months prior to
enrollment.
5. Active herpetic skin lesions or prior complications of herpetic infection (e.g.,
herpetic keratitis or encephalitis).
6. Requires intermittent or chronic systemic (intravenous or oral) treatment with an
antiherpetic drug (e.g., acyclovir), other than intermittent topical use.
7. Previous treatment with talimogene laherparepvec or any other oncolytic virus
8. Prior therapy with tumor vaccine
9. Received live vaccine within 28 days prior to enrollment. 24 | Page Version 6-26-2018
10. Currently receiving treatment with another investigational device or drug study, or <
28 days since ending treatment with another investigational device or drug study(s)
11. Other investigational procedures while participating in this study are excluded.
12. Known to have acute or chronic active hepatitis B infection
13. Known to have acute or chronic active hepatitis C infection
14. History of other malignancy within the past 3 years with the following exceptions:
- adequately treated mucosa associated lymphoid tissue (MALT) tumor
- malignancy treated with curative intent and with no known active disease present
for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the
treating physician
- adequately treated non-melanoma skin cancer, lentigo maligna, stage I or II
cutaneous melanoma, without evidence of disease.
- adequately treated cervical carcinoma in situ without evidence of disease
- adequately treated breast ductal carcinoma in situ without evidence of disease
- prostatic intraepithelial neoplasia without evidence of prostate cancer
- adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
situ
15. Subject has known sensitivity to talimogene laherparepvec or any of its components to
be administered during dosing.
16. Female subject is pregnant or breast-feeding, or planning to become pregnant during
study treatment and through 3 months after the last dose of talimogene laherparepvec
17. Female subject of childbearing potential who is unwilling to use acceptable method(s)
of effective contraception during study treatment and through 3 months after the last
dose of talimogene laherparepvec. (Note: Women not of childbearing potential are
defined as: Any female who is post-menopausal [age > 55 years with cessation of menses
for 12 or more months or less than 55 years but not spontaneous menses for at least 2
years or less than 55 years and spontaneous menses within the past 1 year, but
currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with
postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating
hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according
to the definition of "postmenopausal range" for the laboratory involved] or who have
had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 25 | Page
Version 6-26-2018
18. Sexually active subjects and their partners unwilling to use male latex condom to
avoid potential viral transmission during sexual contact while on treatment and within
30 days after treatment with talimogene laherparepvec.
19. Subject who is unwilling to minimize exposure with his/her blood or other body fluids
to individuals who are at higher risks for HSV-1 induced complications such as
immunosuppressed individuals, individuals known to have HIV infection, 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.
