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

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

Population: 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.

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.

Population: 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.

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.

Population: 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.

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.

Population: 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.

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.

Population: 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.

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.

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

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.

Population: 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.

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.

Population: 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.

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.

Population: 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.