Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer

The objective is to evaluate the efficacy and safety of treatment with chemoradiation (CRT)
plus talimogene laherparepvec compared to CRT alone in previously untreated patients with
locally advanced squamous cell carcinoma of the head and neck (SCCHN) for which surgical
resection is not clinical indicated. The efficacy endpoints of the study aim to demonstrate
overall clinical benefit for patients treated with talimogene laherparepvec as compared to
CRT alone.

Inclusion Criteria:

1. Male or female ≥ 18 years

2. Eastern Co-Operative Oncology Group (ECOG) Performance Status ≤ 1

3. Histological evidence (from the primary lesion and/or lymph nodes) of squamous cell
carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx

4. Stage III or IV disease (T2N2-3M0, T3-4N1-3M0)

5. No evidence of distant metastases by computed tomography (CT) or positron emission
tomography (PET)/CT scan

6. Life expectancy > 4 months

7. Neutrophil count ≥ 2,000/mm^3

8. Platelet count ≥ 100,000/mm^3

9. Hemoglobin ≥ 10 g/dL

10. Bilirubin ≤ 1.5 times upper limit of normal (ULN)

11. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN

12. Alkaline phosphatase ≤ 2.5 times ULN

13. Creatinine clearance ≥ 60 mL/min

14. Female patients of child-bearing potential (i.e. not surgically sterile, or not
having spontaneous amenorrhea for at least 12 months) must agree to use an effective
form of contraception during the treatment phase of the study.

15. Male patients must agree to use a condom with spermicide or their female partner must
use an effective method of birth control.

16. Provide written informed consent in accordance with all applicable regulations and
follow the study procedures. Patients must be capable of understanding the
investigational nature, potential risks and benefits of the study.

Exclusion Criteria:

1. Prior treatment for locally advanced SCCHN (No prior surgery for SCCHN except nodal
sampling or biopsy for study disease).

2. Patients with T1-2N1 or T1N2-3.

3. Pre-existing peripheral neuropathy ≥ Grade 2 (motor or sensory).

4. Weight loss > 20% of body weight within 3 months of screening (unless purposeful).

5. Surgery ≤ 28 days before randomization with the exception of feeding tube placement,
dental extractions, central venous catheter placement, biopsies and nodal sampling.

6. Cancer of the nasopharynx, sinus, salivary gland or skin.

7. Previous radical radiation therapy (RT) to the head and neck region, excluding
superficial RT for a non-melanomatous skin cancer.

8. Prior cancers, except: those diagnosed > 5 years ago with no evidence of disease
recurrence and clinical expectation of recurrence of less than 5%; or successfully
treated non-melanoma skin cancer; or carcinoma in situ of the cervix.

9. Significant intercurrent illness that will interfere with the chemotherapy or
radiation therapy such as human immunodeficiency (HIV) infection, cardiac failure,
pulmonary compromise (chronic obstructive pulmonary disease, pneumonia or respiratory
decompensation) resulting in hospitalization within 12 months of screening, or active
infection.

10. Any significant cardiac disease (e.g., New York Heart Association (NYHA) Class 3 or
4; myocardial infarction within the past 6 months; unstable angina; coronary
angioplasty or coronary artery bypass graft (CABG) within the past 6 months; or
uncontrolled atrial or ventricular cardiac arrhythmias..

11. High risk for poor compliance with therapy or follow up as assessed by the
investigator.

12. Active herpes labialis, other lesions due to herpes simplex virus type I (HSV1) or
dermatoses involving or within 50 cm of the lesions to be injected; active HSV1
lesions must have resolved before talimogene laherparepvec is injected.

13. Prior systemic chemotherapy for any type of cancer.

14. Patients for whom radiation therapy is contraindicated.

15. Pregnant or breast-feeding female. Confirmation that women of child-bearing potential
are not pregnant. A negative serum β- human chorionic gonadotropin (β-hCG) pregnancy
test result must be obtained during the screening period.

16. Currently enrolled and receiving an investigational agent in a clinical research
study or received an investigational agent for any reason within 4 weeks prior to
screening.

17. Require intermittent or chronic treatment with an anti-herpetic drug (e.g.,
acyclovir), other than intermittent topical use.