Talimogene Laherparepvec With Pembrolizumab for Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY232 / KEYNOTE-137) (MASTERKEY232)

• ClinicalTrials.gov Identifier: NCT02626000
• Recruitment Status: Completed
• First Posted: December 10, 2015
• Results First Posted: June 10, 2019
• Last Update Posted: September 8, 2021
• Sponsor: Amgen
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Amgen

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma of the Head and Neck
• Interventions: Drug: Talimogene Laherparepvec; Biological: Pembrolizumab
• Enrollment: 36

Participant Flow

Recruitment Details	This study was conducted at 19 centers in Australia, Canada, Europe, and the United States. This study was designed to be conducted in 2 parts (phase 1b and phase 3). A decision was made not to initiate the phase 3 part of the study.
Pre-assignment Details

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Period Title: Overall Study
Started	36
Completed	6
Not Completed	30
Reason Not Completed
Decision by Sponsor	1
Death	29

Baseline Characteristics

Arm/Group Title		Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description		Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Baseline Participants		36
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	36 participants
		60.8 (10.8)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	< 65 years	21 58.3%
	≥ 65 years	15 41.7%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	Female	7 19.4%
	Male	29 80.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	Hispanic or Latino	2 5.6%
	Not Hispanic or Latino	34 94.4%
	Unknown or Not Reported	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 2.8%
	Black (or African American)	1 2.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	White	33 91.7%
	Other	1 2.8%
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	0 (Fully active)	9 25.0%
	1 (Restricted but ambulatory)	27 75.0%
		[1] Measure Description: A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care, unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.
Herpes Simplex Virus Status; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	Negative	5 13.9%
	Positive	22 61.1%
	Unknown	9 25.0%
Primary Tumor Site; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	Oropharynx	9 25.0%
	Larynx	4 11.1%
	Oral Cavity	20 55.6%
	Hypopharynx	3 8.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Dose Limiting Toxicity (DLT)
Description	The following toxicities (graded per the Common Terminology Criteria for Adverse Events v 4.0) were considered DLTs if judged by the investigator to be related to either study drug: grade 4 non-hematologic (non-laboratory) toxicity; ≥ grade 3 pneumonitis; grade 3 non-hematologic toxicity for > 3 days with optimal supportive care; grade 3 fatigue was not classified as DLT, regardless of duration; any ≥ grade 3 non-hematologic laboratory value if: medical intervention was required, the abnormality led to hospitalization, or the abnormality persisted at ≥ grade 3 for > 1 week unless deemed not clinically important by investigator and sponsor; grade 3 or 4 febrile neutropenia; thrombocytopenia < 25 x 10⁹/L associated with bleeding event requiring intervention; serious herpetic event: herpetic encephalitis, encephalomyelitis, or disseminated herpetic infection; grade 5 toxicity; other intolerable toxicity leading to permanent discontinuation of either study drug.
Time Frame	First 6 weeks after the initial administration of talimogene laherparepvec and pembrolizumab in combination

Outcome Measure Data

Analysis Population Description

The DLT analysis set included DLT-evaluable participants who had the opportunity to be on treatment for at least 6 weeks and had received at least 2 doses of talimogene laherparepvec and 2 doses of pembrolizumab in combination, or who had a DLT during the DLT evaluation period after at least 1 dose of both study drugs in combination.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	16
Measure Type: Count of Participants; Unit of Measure: Participants
	1 6.3%

2. Secondary Outcome

Title	Objective Response Rate
Description	Objective response rate was defined as the percentage of participants with a best overall response of complete response or partial response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required. Analyses are presented below for both the unconfirmed and confirmed results.
Time Frame	Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.

Outcome Measure Data

Analysis Population Description

The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	32
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Confirmed Response	9.4; (2.0 to 25.0)
Unconfirmed Response	15.6; (5.3 to 32.8)

3. Secondary Outcome

Title	Complete Response Rate
Description	Complete response rate (iCRR) was defined as the percentage of participants with a best overall response of complete response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Analyses are presented below for both the unconfirmed and confirmed results.
Time Frame	Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.

Outcome Measure Data

Analysis Population Description

The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	32
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Confirmed Response	0.0; (0.0 to 10.9)
Unconfirmed Response	0.0; (0.0 to 10.9)

4. Secondary Outcome

Title	Best Overall Confirmed Response
Description	Best overall visit response of iCR, iPR, stable disease (iSD), progressive disease (iPD) or unevaluable (iUE) based on investigator assessment using irRECIST. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new). Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor size ≥ 30% relative to baseline. iPD: Increase in tumor size ≥ 20% and at least 5 mm absolute increase compared to nadir or qualitative worsening of non-target lesions or a new lesion. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD. iUE: Any baseline lesion which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor. Not Done: Radiographic imaging was not performed to evaluate the response. iCR, iPR, and iPD required confirmation by a consecutive assessment at least 4 weeks after first documentation.
Time Frame	Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.

Outcome Measure Data

Analysis Population Description

The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	32
Measure Type: Count of Participants; Unit of Measure: Participants
Complete Response (iCR)	0 0.0%
Partial Response (iPR)	3 9.4%
Stable Disease (iSD)	10 31.3%
Progressive Disease (iPD)	4 12.5%
Unevaluable (iUE)	6 18.8%
Not Done	9 28.1%

5. Secondary Outcome

Title	Duration of Confirmed Response
Description	Duration of response (iDOR) per irRECIST was defined as the time from the date of an initial response of iCR or iPR that was subsequently confirmed to the earlier of a participant overall response of iPD or death. Participants who did not end their response at the time of analysis were censored at their last evaluable tumor assessment.
Time Frame	Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy, with a best response of iCR or iPR.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	3
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)

[1]

Could not be estimated due to the low number of events

6. Secondary Outcome

Title	Disease Control Rate
Description	Disease control rate (iDCR) was defined as the percentage of participants with a best overall response of iCR or iPR or iSD assessed by the investigator using irRECIST. Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required. Stable disease (iSD): Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD. Analyses are presented below for both the unconfirmed and confirmed results.
Time Frame	Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.

Outcome Measure Data

Analysis Population Description

The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	32
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Confirmed Response	40.6; (23.7 to 59.4)
Unconfirmed Response	40.6; (23.7 to 59.4)

7. Secondary Outcome

Title	Progression Free Survival
Description	Progression-free survival (iPFS) per irRECIST was defined as the interval from first dose to the earlier of a participant overall response of iPD or death from any cause; otherwise, iPFS was censored at the last evaluable tumor assessment. The initial date of an iPD that was consecutively confirmed was used.
Time Frame	Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.

Outcome Measure Data

Analysis Population Description

The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	32
Median (95% Confidence Interval); Unit of Measure: months
	3.0; (2.0 to 5.8)

8. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as the interval from first dose to the event of death from any cause; otherwise, OS was censored at the date the participant was last known to be alive.
Time Frame	Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.

Outcome Measure Data

Analysis Population Description

The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	32
Median (95% Confidence Interval); Unit of Measure: months
	5.2; (2.1 to 11.4)

9. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	The severity of adverse events was assessed by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and based on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event is an AE that met at least 1 of the following serious criteria: fatal; life threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event.
Time Frame	From first dose of study drug to 30 days after last dose; the median (range) duration of treatment was 5.6 (0.1 to 75.3) weeks for talimogene laherparepvec and 6.1 (0.1, 105.3) weeks for pembrolizumab.

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab.

Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description:	Talimogene laherparepvec (T-VEC) was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
Overall Number of Participants Analyzed	36
Measure Type: Count of Participants; Unit of Measure: Participants
All treatment-emergent adverse events	36 100.0%
Treatment-emergent adverse events grade ≥ 2	36 100.0%
Treatment-emergent adverse events grade ≥ 3	26 72.2%
Treatment-emergent adverse events grade ≥ 4	11 30.6%
Serious adverse events	26 72.2%
AE leading to discontinuation of T-VEC	6 16.7%
AE leading to discontinuation of pembrolizumab	6 16.7%
Fatal adverse events	7 19.4%
Talimogene laherparepvec-related AEs	21 58.3%
Pembrolizumab-related AEs	21 58.3%

Adverse Events

Time Frame	From first dose of study drug to 30 days after last dose; the median (range) duration of treatment was 5.6 (0.1 to 75.3) weeks for talimogene laherparepvec and 6.1 (0.1, 105.3) weeks for pembrolizumab.
Adverse Event Reporting Description	Serious adverse event and other adverse events are reported for all participants who received at least one dose of study drug.
Arm/Group Title	Talimogene Laherparepvec + Pembrolizumab
Arm/Group Description	Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
All-Cause Mortality
	Talimogene Laherparepvec + Pembrolizumab
	Affected / at Risk (%)
Total	29/36 (80.56%)
Serious Adverse Events
	Talimogene Laherparepvec + Pembrolizumab
	Affected / at Risk (%)
Total	26/36 (72.22%)
Gastrointestinal disorders
Dysphagia † 1	2/36 (5.56%)
Odynophagia † 1	1/36 (2.78%)
General disorders
Chills † 1	1/36 (2.78%)
General physical health deterioration † 1	2/36 (5.56%)
Mucosal haemorrhage † 1	1/36 (2.78%)
Pain † 1	1/36 (2.78%)
Pyrexia † 1	2/36 (5.56%)
Hepatobiliary disorders
Hepatitis † 1	1/36 (2.78%)
Infections and infestations
Bronchitis † 1	1/36 (2.78%)
Localised infection † 1	1/36 (2.78%)
Pneumonia † 1	2/36 (5.56%)
Respiratory tract infection † 1	1/36 (2.78%)
Staphylococcal infection † 1	1/36 (2.78%)
Tracheitis † 1	1/36 (2.78%)
Wound infection † 1	1/36 (2.78%)
Lower respiratory tract infection † 1	1/36 (2.78%)
Sepsis † 1	1/36 (2.78%)
Wound infection bacterial † 1	1/36 (2.78%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	1/36 (2.78%)
Toxicity to various agents † 1	1/36 (2.78%)
Tracheal obstruction † 1	1/36 (2.78%)
Tracheostomy malfunction † 1	1/36 (2.78%)
Metabolism and nutrition disorders
Decreased appetite † 1	1/36 (2.78%)
Hypercalcaemia † 1	2/36 (5.56%)
Hypoglycaemia † 1	1/36 (2.78%)
Euglycaemic diabetic ketoacidosis † 1	1/36 (2.78%)
Musculoskeletal and connective tissue disorders
Back pain † 1	1/36 (2.78%)
Musculoskeletal pain † 1	1/36 (2.78%)
Intervertebral disc protrusion † 1	1/36 (2.78%)
Musculoskeletal chest pain † 1	1/36 (2.78%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of head and neck † 1	2/36 (5.56%)
Tumour pain † 1	1/36 (2.78%)
Tumour haemorrhage † 1	1/36 (2.78%)
Nervous system disorders
Cerebrovascular accident † 1	1/36 (2.78%)
Somnolence † 1	1/36 (2.78%)
Cerebral venous sinus thrombosis † 1	1/36 (2.78%)
Psychiatric disorders
Confusional state † 1	1/36 (2.78%)
Delirium † 1	1/36 (2.78%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	1/36 (2.78%)
Pneumonia aspiration † 1	2/36 (5.56%)
Respiratory arrest † 1	1/36 (2.78%)
Stridor † 1	1/36 (2.78%)
Skin and subcutaneous tissue disorders
Eczema † 1	1/36 (2.78%)
Vascular disorders
Arterial haemorrhage † 1	1/36 (2.78%)
Hypotension † 1	1/36 (2.78%)
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Talimogene Laherparepvec + Pembrolizumab
	Affected / at Risk (%)
Total	33/36 (91.67%)
Blood and lymphatic system disorders
Anaemia † 1	6/36 (16.67%)
Ear and labyrinth disorders
Ear pain † 1	3/36 (8.33%)
Endocrine disorders
Hypothyroidism † 1	3/36 (8.33%)
Gastrointestinal disorders
Constipation † 1	9/36 (25.00%)
Diarrhoea † 1	5/36 (13.89%)
Dysphagia † 1	8/36 (22.22%)
Nausea † 1	7/36 (19.44%)
Odynophagia † 1	3/36 (8.33%)
Oral pain † 1	4/36 (11.11%)
Stomatitis † 1	2/36 (5.56%)
Vomiting † 1	5/36 (13.89%)
General disorders
Asthenia † 1	5/36 (13.89%)
Face oedema † 1	2/36 (5.56%)
Fatigue † 1	10/36 (27.78%)
Influenza like illness † 1	5/36 (13.89%)
Injection site pain † 1	3/36 (8.33%)
Pyrexia † 1	12/36 (33.33%)
Infections and infestations
Lower respiratory tract infection † 1	4/36 (11.11%)
Oral candidiasis † 1	2/36 (5.56%)
Rhinitis † 1	2/36 (5.56%)
Skin infection † 1	3/36 (8.33%)
Upper respiratory tract infection † 1	2/36 (5.56%)
Investigations
Body temperature increased † 1	3/36 (8.33%)
Weight decreased † 1	2/36 (5.56%)
Metabolism and nutrition disorders
Decreased appetite † 1	5/36 (13.89%)
Hypokalaemia † 1	2/36 (5.56%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain † 1	3/36 (8.33%)
Neck pain † 1	4/36 (11.11%)
Pain in extremity † 1	2/36 (5.56%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain † 1	3/36 (8.33%)
Nervous system disorders
Headache † 1	6/36 (16.67%)
Psychiatric disorders
Confusional state † 1	2/36 (5.56%)
Insomnia † 1	4/36 (11.11%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	7/36 (19.44%)
Dyspnoea † 1	12/36 (33.33%)
Haemoptysis † 1	2/36 (5.56%)
Orthopnoea † 1	2/36 (5.56%)
Productive cough † 1	2/36 (5.56%)
Increased bronchial secretion † 1	2/36 (5.56%)
Skin and subcutaneous tissue disorders
Pruritus † 1	2/36 (5.56%)
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Amgen Inc.
• Phone: 866-572-6436
• EMail: medinfo@amgen.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Harrington KJ, Kong A, Mach N, Chesney JA, Fernandez BC, Rischin D, Cohen EEW, Radcliffe HS, Gumuscu B, Cheng J, Snyder W, Siu LL. Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Clin Cancer Res. 2020 Oct 1;26(19):5153-5161. doi: 10.1158/1078-0432.CCR-20-1170. Epub 2020 Jul 15.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02626000
• Other Study ID Numbers: 20130232; 20130232 / KEYNOTE-137 ( Other Identifier: Merck / Amgen ); 2015-003011-38 ( EudraCT Number )
• First Submitted: November 18, 2015
• First Posted: December 10, 2015
• Results First Submitted: October 19, 2018
• Results First Posted: June 10, 2019
• Last Update Posted: September 8, 2021