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

• Sponsor: BioVex Limited (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01161498
• Collaborator: Amgen (Industry)
• Enrollment: 5
• Locations: 6
• Arms: 2
• Duration (Months): 8
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is being conducted to learn about the safety and risks of using talimogene laherparepvec to treat patients with head and neck cancer and to see if talimogene laherparepvec and chemoradiation together can destroy the tumours versus the use of chemoradiation alone. This study may provide information on the usefulness of talimogene laherparepvec combined with chemoradiation as a future treatment for head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma; Head and Neck Cancer	Biological: Talimogene Laherparepvec; Radiation: Radiation; Drug: Cisplatin	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized Trial of Concurrent Cisplatin & Radiotherapy With Or Without ONCOVEX^GM-CSF In Previously Untreated Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Radiation: Radiation; 70 grays of radiation administered in 35 fractions over 7 weeks; Drug: Cisplatin; Administered by intravenous infusion
Experimental: 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 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; Administered by intratumoral injection; Other Names: OncoVEX^GM-CSF IMLYGIC ; Radiation: Radiation; 70 grays of radiation administered in 35 fractions over 7 weeks; Drug: Cisplatin; Administered by intravenous infusion

Outcome Measures

Primary Outcome Measures

1. 2-year Event-free Survival [2 years]

   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.

Secondary Outcome Measures

1. Clinical Objective Response (cOR) [End of trial; the maximum time on study was 20 weeks.]

   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.

2. Metabolic Complete Response (mCR) [End of study; the maximum time on study was 20 weeks.]

   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.

3. Pathologic Complete Response (mCR) [Up to Week 20]

   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.

4. Time to Locoregional Failure [Up to 27 months]

   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.

5. Time to Distant Failure [Up to 27 months]

   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.

6. Time to Any Failure [Up to 27 months]

   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.

7. Overall Survival [Up to 5 years after chemoradiotherapy]

   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.

8. Disease-specific Survival [Up to 5 years after chemoradiotherapy]

   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.

9. Participants With N1-2 Disease at Baseline Requiring Neck Dissection [Weeks 19 - 21]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Clinical Research of Indiana	Indianapolis	Indiana	United States	46260
2	James Graham Brown Cancer Center, University of Louisville	Louisville	Kentucky	United States	40202
3	Gabrail Cancer Center	Canton	Ohio	United States	44718
4	Medical Univesity of South Carolina	Charleston	South Carolina	United States	29425
5	VCU Massey Cancer Center	Richmond	Virginia	United States	23298
6	The Royal Marsden Hospital	London		United Kingdom	SE1 7EH

Sponsors and Collaborators

• BioVex Limited
• Amgen

Investigators

• Principal Investigator: Kevin Harrington, MD, Royal Marsden, UK

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioVex Limited
• ClinicalTrials.gov Identifier: NCT01161498
• Other Study ID Numbers: 006/09; 20110130
• First Posted: Jul 13, 2010
• Last Update Posted: Feb 8, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by BioVex Limited: squamous cell; OncoVEX^GM-CSF; Oncovex; chemoradiation; Cisplatin
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Talimogene laherparepvec

Study Results

Participant Flow

Recruitment Details	This study was open to patients with advanced, non-metastatic, stage III or IV squamous cell carcinoma of the head and neck (SCCHN).

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	3	2
COMPLETED	3	1
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	3	2	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	1 50%	4 80%
>=65 years	0 0%	1 50%	1 20%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	1 20%
Male	2 66.7%	2 100%	4 80%

Outcome Measures

1. Primary Outcome

Title	2-year Event-free Survival
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	0	0

2. Secondary Outcome

Title	Clinical Objective Response (cOR)
Description	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.
Time Frame	End of trial; the maximum time on study was 20 weeks.

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	3	2
Clinical Complete Response (cCR)	2 66.7%	1 50%
Clinical Partial Response (cPR)	0 0%	0 0%
Progressive Disease	1 33.3%	0 0%
Unevaluable	0 0%	1 50%

3. Secondary Outcome

Title	Metabolic Complete Response (mCR)
Description	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.
Time Frame	End of study; the maximum time on study was 20 weeks.

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	3	2
Metabolic Complete Response (mCR)	1 33.3%	1 50%
Metabolic Partial Response (mPR)	0 0%	0 0%
Metabolic Progressive Disease (mPD)	1 33.3%	0 0%
Stable Metabolic Response (mSD)	0 0%	0 0%
Unevaluable	1 33.3%	1 50%

4. Secondary Outcome

Title	Pathologic Complete Response (mCR)
Description	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.
Time Frame	Up to Week 20

Outcome Measure Data

Analysis Population Description

Randomized participants who had protocol-specified surgery

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	1	0
Number [participants]	0 0%

5. Secondary Outcome

Title	Time to Locoregional Failure
Description	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.
Time Frame	Up to 27 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	0	0

6. Secondary Outcome

Title	Time to Distant Failure
Description	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.
Time Frame	Up to 27 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	0	0

7. Secondary Outcome

Title	Time to Any Failure
Description	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.
Time Frame	Up to 27 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	0	0

8. Secondary Outcome

Title	Overall Survival
Description	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.
Time Frame	Up to 5 years after chemoradiotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	0	0

9. Secondary Outcome

Title	Disease-specific Survival
Description	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.
Time Frame	Up to 5 years after chemoradiotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	0	0

10. Secondary Outcome

Title	Participants With N1-2 Disease at Baseline Requiring Neck Dissection
Description	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.
Time Frame	Weeks 19 - 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Radiation/Cisplatin	Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.	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.
Measure Participants	0	0

Adverse Events

Time Frame	20 weeks
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Radiation/Cisplatin		Talimogene Laherparepvec + Radiation/Cisplatin
Arm/Group Description	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.		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.
All Cause Mortality
	Radiation/Cisplatin		Talimogene Laherparepvec + Radiation/Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Radiation/Cisplatin		Talimogene Laherparepvec + Radiation/Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/2 (100%)
Gastrointestinal disorders
Mouth haemorrhage	1/3 (33.3%)		0/2 (0%)
Infections and infestations
Lung infection	0/3 (0%)		1/2 (50%)
Urinary tract infection	0/3 (0%)		1/2 (50%)
Metabolism and nutrition disorders
Dehydration	1/3 (33.3%)		0/2 (0%)
Hyperglycaemia	0/3 (0%)		1/2 (50%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	0/3 (0%)		1/2 (50%)
Renal and urinary disorders
Renal failure acute	0/3 (0%)		1/2 (50%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/3 (0%)		1/2 (50%)
Other (Not Including Serious) Adverse Events
	Radiation/Cisplatin		Talimogene Laherparepvec + Radiation/Cisplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		2/2 (100%)
Blood and lymphatic system disorders
Anaemia	2/3 (66.7%)		0/2 (0%)
Neutropenia	1/3 (33.3%)		0/2 (0%)
Gastrointestinal disorders
Abdominal pain	0/3 (0%)		2/2 (100%)
Constipation	1/3 (33.3%)		1/2 (50%)
Diarrhoea	1/3 (33.3%)		2/2 (100%)
Dry mouth	0/3 (0%)		1/2 (50%)
Dyspepsia	1/3 (33.3%)		0/2 (0%)
Dysphagia	0/3 (0%)		1/2 (50%)
Gastrooesophageal reflux disease	0/3 (0%)		1/2 (50%)
Impaired gastric emptying	0/3 (0%)		1/2 (50%)
Nausea	1/3 (33.3%)		2/2 (100%)
Odynophagia	0/3 (0%)		1/2 (50%)
Oral dysaesthesia	0/3 (0%)		1/2 (50%)
Saliva altered	1/3 (33.3%)		0/2 (0%)
Salivary duct inflammation	1/3 (33.3%)		2/2 (100%)
Stomatitis	3/3 (100%)		1/2 (50%)
Vomiting	2/3 (66.7%)		1/2 (50%)
General disorders
Catheter site erythema	1/3 (33.3%)		0/2 (0%)
Fatigue	1/3 (33.3%)		1/2 (50%)
Pain	1/3 (33.3%)		0/2 (0%)
Infections and infestations
Lung infection	0/3 (0%)		1/2 (50%)
Oral candidiasis	0/3 (0%)		1/2 (50%)
Postoperative wound infection	0/3 (0%)		1/2 (50%)
Upper respiratory tract infection	1/3 (33.3%)		0/2 (0%)
Urinary tract infection	0/3 (0%)		1/2 (50%)
Investigations
Blood creatinine increased	0/3 (0%)		1/2 (50%)
Body temperature increased	1/3 (33.3%)		0/2 (0%)
Electrocardiogram QT prolonged	0/3 (0%)		1/2 (50%)
Weight decreased	1/3 (33.3%)		1/2 (50%)
Metabolism and nutrition disorders
Dehydration	1/3 (33.3%)		1/2 (50%)
Hypercalcaemia	1/3 (33.3%)		0/2 (0%)
Hypomagnesaemia	1/3 (33.3%)		0/2 (0%)
Hyponatraemia	1/3 (33.3%)		0/2 (0%)
Hypophagia	0/3 (0%)		1/2 (50%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/3 (0%)		1/2 (50%)
Musculoskeletal chest pain	0/3 (0%)		1/2 (50%)
Nervous system disorders
Dizziness	0/3 (0%)		1/2 (50%)
Dysgeusia	0/3 (0%)		1/2 (50%)
Psychiatric disorders
Delirium	0/3 (0%)		1/2 (50%)
Depression	0/3 (0%)		1/2 (50%)
Insomnia	0/3 (0%)		1/2 (50%)
Renal and urinary disorders
Dysuria	0/3 (0%)		1/2 (50%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/3 (33.3%)		1/2 (50%)
Hypoxia	0/3 (0%)		1/2 (50%)
Laryngeal oedema	0/3 (0%)		1/2 (50%)
Nasal congestion	1/3 (33.3%)		0/2 (0%)
Oropharyngeal pain	0/3 (0%)		1/2 (50%)
Pleural effusion	0/3 (0%)		1/2 (50%)
Pneumothorax	0/3 (0%)		1/2 (50%)
Productive cough	1/3 (33.3%)		1/2 (50%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/3 (0%)		1/2 (50%)
Erythema	1/3 (33.3%)		0/2 (0%)
Skin ulcer	0/3 (0%)		1/2 (50%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.