Study of Safety and Efficacy of Talimogene Laherparepvec... | NCT01161498

ID	Type	Description	Link
20110130	Other Identifier	Amgen Inc.

Name	Class
Amgen	INDUSTRY

Label	Type	Description	Intervention Names
Radiation/Cisplatin	Active Comparator	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Radiation: Radiation Drug: Cisplatin
Talimogene Laherparepvec + Radiation/Cisplatin	Experimental	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.	Biological: Talimogene Laherparepvec Radiation: Radiation Drug: Cisplatin

Name	Type	Description	Arm Group Labels	Other Names
Talimogene Laherparepvec	Biological	Administered by intratumoral injection	Talimogene Laherparepvec + Radiation/Cisplatin

Measure	Description	Time Frame
2-year Event-free Survival	Event-free survival is defined as the time from randomization until the first evidence of relapse, disease progression (local, regional, metastatic, or second primary), or death from any cause. Because this study was terminated with only 5 participants enrolled, and the study was terminated in the first year, this endpoint was not analyzed.	2 years

Measure	Description	Time Frame
Clinical Objective Response (cOR)	Tumor response was assessed by computed tomography (CT) scan according to a modified version of the revised Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1). Objective response is defined as achieving a clinical partial response (cPR) or complete response (cCR). cCR is defined as disappearance of all baseline lesions. Any pathological lymph nodes must have a reduction in short axis to < 10 mm. cPR is defined as at least a 30% decrease in the sum of diameters of baseline lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of baseline lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or the appearance of any new lesions. Because this study was terminated with 5 patients enrolled, data for this endpoint were summarized in by-patient listings only and the cOR rate was not calculated. Therefore a summary of response at the end of study is reported.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female ≥ 18 years
Eastern Co-Operative Oncology Group (ECOG) Performance Status ≤ 1
Histological evidence (from the primary lesion and/or lymph nodes) of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
Stage III or IV disease (T2N2-3M0, T3-4N1-3M0)
No evidence of distant metastases by computed tomography (CT) or positron emission tomography (PET)/CT scan
Life expectancy > 4 months
Neutrophil count ≥ 2,000/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10 g/dL
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Creatinine clearance ≥ 60 mL/min
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.
Male patients must agree to use a condom with spermicide or their female partner must use an effective method of birth control.
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:

Prior treatment for locally advanced SCCHN (No prior surgery for SCCHN except nodal sampling or biopsy for study disease).
Patients with T1-2N1 or T1N2-3.
Pre-existing peripheral neuropathy ≥ Grade 2 (motor or sensory).
Weight loss > 20% of body weight within 3 months of screening (unless purposeful).
Surgery ≤ 28 days before randomization with the exception of feeding tube placement, dental extractions, central venous catheter placement, biopsies and nodal sampling.
Cancer of the nasopharynx, sinus, salivary gland or skin.
Previous radical radiation therapy (RT) to the head and neck region, excluding superficial RT for a non-melanomatous skin cancer.
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.
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.
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..
High risk for poor compliance with therapy or follow up as assessed by the investigator.
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.
Prior systemic chemotherapy for any type of cancer.
Patients for whom radiation therapy is contraindicated.
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.
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.
Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use.

Name	Affiliation	Role
Kevin Harrington, MD	Royal Marsden, UK	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Investigative Clinical Research of Indiana		Indianapolis	Indiana	46260	United States
James Graham Brown Cancer Center, University of Louisville

ID	Title	Description
FG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
FG001	Talimogene Laherparepvec + Radiation/Cisplatin

ID	Title	Description
BG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
BG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0012 BG0025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

2-year Event-free Survival

Event-free survival is defined as the time from randomization until the first evidence of relapse, disease progression (local, regional, metastatic, or second primary), or death from any cause. Because this study was terminated with only 5 participants enrolled, and the study was terminated in the first year, this endpoint was not analyzed.

Posted

2 years

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Units	Counts
Participants	OG0000 OG0010

Secondary

Clinical Objective Response (cOR)

Tumor response was assessed by computed tomography (CT) scan according to a modified version of the revised Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1). Objective response is defined as achieving a clinical partial response (cPR) or complete response (cCR). cCR is defined as disappearance of all baseline lesions. Any pathological lymph nodes must have a reduction in short axis to < 10 mm. cPR is defined as at least a 30% decrease in the sum of diameters of baseline lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of baseline lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or the appearance of any new lesions.

Because this study was terminated with 5 patients enrolled, data for this endpoint were summarized in by-patient listings only and the cOR rate was not calculated. Therefore a summary of response at the end of study is reported.

All randomized participants

Posted

Number

participants

End of trial; the maximum time on study was 20 weeks.

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Secondary

Metabolic Complete Response (mCR)

Response to therapy was assessed using [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging to detect metabolically active tumors.

Metabolic complete response (mCR) is defined as complete disappearance of FDG uptake attributable to tumor compared to baseline scan.

Partial metabolic response (mPR) is defined as a > 40% decrease in specific uptake compared to the initial value in over half of the lesions.

Disease progression (mPD) is defined as a specific uptake increase in any lesion, appearance of new lesions, or presence of extended areas of disease activity.

Stable metabolic response (mSD) is defined as a decrease in uptake < 40% of the initial value of over half the lesions.

Because this study was terminated with 5 patients enrolled, data for this endpoint were summarized in by-patient listings only and the metabolic complete response rate was not calculated. Therefore a summary of metabolic response at end of study is reported.

All randomized participants

Posted

Number

participants

End of study; the maximum time on study was 20 weeks.

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Secondary

Pathologic Complete Response (mCR)

Response to therapy was assessed histopathologically from biopsies taken at surgery for those participants who had surgery prior to Week 22.

If no viable tumor cells were identified in surgical specimens (where the patient had surgery) the patient was classified as having a pathological complete response (pCR), and if viable tumor cells were identified, the patient was classified as having an incomplete pathologic response.

Because this study was terminated with 5 patients enrolled, data for this endpoint were summarized in by-patient listings only and the pathologic complete response rate was not calculated. Therefore a summary of participants with a pathologic complete response before the end of study is reported.

Randomized participants who had protocol-specified surgery

Posted

Number

participants

Up to Week 20

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Secondary

Time to Locoregional Failure

Locoregional failure is defined as disease progression in the head and neck area at any time following completion of chemoradiotherapy.

Because this study was terminated with 5 subjects enrolled, time to locoregional failure was not analyzed.

Posted

Up to 27 months

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Units	Counts
Participants

Secondary

Time to Distant Failure

Distant failure is defined as disease progression at any site other than the head and neck area at any time following completion of chemoradiotherapy.

Because this study was terminated with 5 participants enrolled, time to distant failure was not analyzed.

Posted

Up to 27 months

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Units	Counts
Participants

Secondary

Time to Any Failure

Any failure is defined as disease progression at any site at any time following completion of chemoradiotherapy.

Because this study was terminated with 5 participants enrolled, time to any failure was not analyzed.

Posted

Up to 27 months

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Units	Counts
Participants

Secondary

Overall Survival

Overall survival is defined as the time from randomization to death from any cause.

Because this study was terminated with 5 participants enrolled, overall survival was not analyzed.

Posted

Up to 5 years after chemoradiotherapy

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Units	Counts
Participants

Secondary

Disease-specific Survival

Disease-specific survival is defined as the time from randomization to death of the patient due to the cancer under study.

Because this study was terminated with 5 participants enrolled, disease-specific survival was not analyzed.

Posted

Up to 5 years after chemoradiotherapy

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Units	Counts
Participants

Secondary

Participants With N1-2 Disease at Baseline Requiring Neck Dissection

Participants with Baseline Nl or N2 disease (lymph node metastasis not more than 6 cm in greatest dimension) with persistent disease as determined at the post chemoradiotherapy assessment of response were to proceed to neck dissection as permitted by the institution no later than Week 22. Since this study terminated prematurely neck dissection data were not collected or analyzed.

Posted

Weeks 19 - 21

ID	Title	Description
OG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.
OG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.

Units	Counts

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected3 at risk EG0010 affected2 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0012 affected2 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected2 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0012 affected2 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0012 affected2 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Oral dysaesthesia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Saliva altered	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Salivary duct inflammation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0012 affected2 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected3 at risk EG0011 affected2 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected3 at risk EG0011 affected2 at risk
Catheter site erythema	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Fatigue	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected2 at risk
Pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Lung infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Oral candidiasis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Postoperative wound infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Blood creatinine increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Body temperature increased	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Weight decreased	Investigations	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected2 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected2 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Dizziness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Dysgeusia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Delirium	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Depression	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Insomnia	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Dysuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected2 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0011 affected2 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk

ID	Term
D002294	Carcinoma, Squamous Cell
D006258	Head and Neck Neoplasms

ID	Term
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D018307	Neoplasms, Squamous Cell
D009371	Neoplasms by Site

ID	Term
D055585	Physical Phenomena
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Radiation/Cisplatin	Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.			2	3	3	3
EG001	Talimogene Laherparepvec + Radiation/Cisplatin	The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.			2	2	2	2

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Lung infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected3 at risk EG0010 affected2 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected3 at risk EG0011 affected2 at risk

ID	Term
C000629782	talimogene laherparepvec
D011827	Radiation
D002945	Cisplatin