PHARYNGEAL MUCOSITIS; PHARYNGEAL STENOSIS; This 72-year-old male subject was enrolled in a study. The subject received Bintrafusp Alfa (M7824) (intravenous) 1200 mg from 11th May 2022 to 2nd August 2022, for head and neck cancer.   Co-suspect products included HPV 16-18 (HPV vaccine) for prophylaxis.   The subject's past medical history included knee operation (From 2009), bypass surgery (From 2012), radiation therapy (with weekly Cisplatin in Aug 2017 with complete remission for three years), percutaneous endoscopic gastrostomy and vascular graft. Previously administered products included CISPLATIN with an associated reaction of no adverse event, CARBOPLATIN with an associated reaction of no adverse event, 5-FLUOROURACIL with an associated reaction of no adverse event, PEMBROLIZUMAB with an associated reaction of no adverse event and PEMBROLIZUMAB with an associated reaction of no adverse event. Concurrent medical conditions included hypertension, hyperlipidemia, congestive heart failure, glucose tolerance impaired (On APR-2017), acute kidney injury, hemorrhage from throat, neoplasm recurrence and neoplasm recurrence. Concomitant products included lisinopril, metoprolol succinate, rosuvastatin and paracetamol (Tylenol).   On 30th August 2022, 111 days after the first dose and 28 days after the most recent dose of Bintrafusp Alfa (M7824), the subject developed grade 4 pharyngeal mucositis. Serious criteria included hospitalization. Additional event(s) included grade 4 pharyngeal stenosis on 30th August 2022 with serious criteria of hospitalization. The outcome of pharyngeal mucositis was recovered/resolved on 7th September 2022. The outcome(s) of the additional event(s) included pharyngeal stenosis (recovered/resolved on 7th September 2022).   The investigator considered that there was a reasonable possibility that the pharyngeal mucositis and pharyngeal stenosis may have been caused by Bintrafusp Alfa (M7824). Other possible cause(s) of the pharyngeal mucositis included disease under study and medical condition. Other possible cause(s) of the pharyngeal stenosis included disease under study and other.   Relevant Tests: BLOOD PRESSURE; 03-May-2022; 140/65 mmHg;  CT OF CHEST/ABDOMEN/PELVIS; 03-May-2022; showed no significant change of ground glass centrilobular nodularity/tree in bud in the left lower lobe, a stable mild ground glass nodule in the right lower lobe concerning for infection/aspiration, and mild subcarinal and left retroperitoneal lymphadenopathy.;  HAEMATOCRIT; 16-Aug-2022; not reported;  BLOOD PRESSURE; 30-Aug-2022; 142/68 mmHg;  CT NECK; 29-Aug-2022; which showed further enlargement of left neck mass with probable encasement of left vertebral artery, and increased nodularity of the pharyngeal mucosa.;  CT OF CHEST/ABDOMEN/PELVIS; 29-Aug-2022; no evidence of lung, liver or bone gross metastasis;  NASOPHARYNGOLARYNGOSCOPY; 30-Aug-2022; showed severe crusting mixed with mucous and debris coating entire upper airway which caused pharyngeal stenosis with stridor and difficulty in breathing.;  WBC COUNT; 30-Aug-2022; 8.49 K/mcL;  PLATELET COUNT; 30-Aug-2022; 231 K/mcL; Diagnostic results (unless otherwise stated, normal values were not provided):  On 3rd May 2022, Blood creatinine result was 1.43 unknown (normal low: 0.6, normal high: 1.3), Blood potassium result was 4.5 mmol/L (normal low: 3.5, normal high: 5.1), Blood pressure measurement result was 140/65 unknown, Blood sodium result was 137 mmol/L (normal low: 135, normal high: 148), Blood urea result was 43 unknown (normal low: 7, normal high: 30), Body temperature result was 35.4 unknown, Computerised tomogram result was Not Reported unknown, Haematocrit result was 35.3 % (normal low: 41, normal high: 53), Haemoglobin result was 12.1 g/dL (normal low: 13.9, normal high: 16.3), Heart rate result was 67 unknown, Oxygen saturation result was 99 %, Platelet count result was 157 x10^3/mcL (normal low: 150, normal high: 350), Respiratory rate result was 16 unknown and White blood cell count result was 5.17 x10^3/mcL (normal low: 4.50, normal high: 11). On 16th August 2022, Blood creatinine result was 1.32 unknown (normal low: 0.6, normal high: 1.3), Blood potassium result was 4.1 mmol/L (normal low: 3.5, normal high: 5.1), Blood sodium result was 135 mmol/L (normal low: 135, normal high: 148), Haematocrit result was not reported unknown, Haemoglobin result was 9.1 g/dL (normal low: 13.9, normal high: 16.3), Platelet count result was 238 x10^3/mcL (normal low: 150, normal high: 350) and White blood cell count result was 8.02 x10^3/mcL (normal low: 4.50, normal high: 11). On 29th August 2022, Blood potassium result was 5.1 mmol/L (normal low: 3.5, normal high: 5.1), Blood sodium result was 134 mmol/L (normal low: 135, normal high: 148), Blood urea result was 49 unknown (normal low: 7, normal high: 30), Computerised tomogram result was Not Reported unknown, Computerised tomogram neck result was which showed further enlargement of left neck mass unknown, Haematocrit result was 29.5 % (normal low: 41, normal high: 53), Haemoglobin result was 9.3 g/dL (normal low: 13.9, normal high: 16.3), Platelet count result was 231 x10^3/mcL (normal low: 150, normal high: 350) and White blood cell count result was 8.49 x10^3/mcL (normal low: 4.50, normal high: 11). On 30th August 2022, Blood creatinine result was 1.28 mg/dL, Blood potassium result was 5.1 mmol/L, Blood pressure measurement result was 142/68 unknown, Blood sodium result was 134 mmol/L, Blood urea result was 49 mg/dL, Body temperature result was 36.1 unknown, Haematocrit result was 29.5 %, Haemoglobin result was 9.3 g/dL, Heart rate result was 79 unknown and Nasolaryngoscopy result was showed severe crusting mixed with mucous and debri unknown. On 30th August 2022, Oxygen saturation result was 97 %, Platelet count result was 231 K/mcL unknown, Respiratory rate result was 18 unknown, Respiratory rate result was 19 unknown and White blood cell count result was 8.49 K/mcL unknown. On 1st September 2022, Blood creatinine result was 1.1 unknown (normal low: 0.6, normal high: 1.3), Blood potassium result was 3.8 mmol/L (normal low: 3.5, normal high: 5.1), Blood sodium result was 132 mmol/L (normal low: 135, normal high: 148), Blood urea result was 36 unknown (normal low: 7, normal high: 30), Chest X-ray result was mild left lower lung pneumonia unknown, Haematocrit result was 26.6 % (normal low: 41, normal high: 53), Haemoglobin result was 8.2 g/dL (normal low: 13.9, normal high: 16.3), Platelet count result was 194 x10^3/mcL (normal low: 150, normal high: 350) and White blood cell count result was 15.61 x10^3/mcL (normal low: 4.50, normal high: 11). On 2nd September 2022, Blood creatinine result was 1.1 unknown (normal low: 0.6, normal high: 1.3), Blood potassium result was 4.4 mmol/L (normal low: 3.5, normal high: 5.1), Blood sodium result was 132 mmol/L (normal low: 135, normal high: 148), Blood urea result was 34 unknown (normal low: 7, normal high: 30), Haematocrit result was 28.6 % (normal low: 41, normal high: 53), Haemoglobin result was 9.2 g/dL (normal low: 13.9, normal high: 16.3), Platelet count result was 181 x10^3/mcL (normal low: 150, normal high: 350), Staphylococcus test result was unknown unknown and White blood cell count result was 10.55 x10^3/mcL (normal low: 4.50, normal high: 11). On 3rd September 2022, Blood creatinine result was 1.1 unknown (normal low: 0.6, normal high: 1.3), Blood potassium result was 3.6 mmol/L (normal low: 3.5, normal high: 5.1), Blood sodium result was 136 mmol/L (normal low: 135, normal high: 148) and Blood urea result was 36 unknown (normal low: 7, normal high: 30). On 4th September 2022, Blood creatinine result was 1.1 unknown (normal low: 0.6, normal high: 1.3), Blood potassium result was 3.6 mmol/L (normal low: 3.5, normal high: 5.1), Blood sodium result was 138 mmol/L (normal low: 135, normal high: 148) and Blood urea result was 32 unknown (normal low: 7, normal high: 30). On 5th September 2022, Blood creatinine result was 1 unknown (normal low: 0.6, normal high: 1.3), Blood potassium result was 3.7 mmol/L (normal low: 3.5, normal high: 5.1), Blood sodium result was 137 mmol/L (normal low: 135, normal high: 148) and Blood urea result was 27 unknown (normal low: 7, normal high: 30). On 6th September 2022, Blood creatinine result was 1 unknown (normal low: 0.6, normal high: 1.3), Blood potassium result was 4 mmol/L (normal low: 3.5, normal high: 5.1), Blood sodium result was 132 mmol/L (normal low: 135, normal high: 148) and Blood urea result was 24 unknown (normal low: 7, normal high: 30).                                                                                                    Linked case(s) involving the same subject:  US2022122484   Additional Information: GSK Receipt Date:2-SEP-2022 Case received via MERCK . MERCK received case 2-SEP-2022 and subsequently forwarded to GSK on 8-SEP-2022 Subject id reported as MS200647_0073-101-28 LP Narrative:MS200647_0073: 20-C-0104,On an unknown date in Aug 2017, the subject was initially diagnosed with squamous cell carcinoma of oropharynx. Post multiple prior lines of therapy including radiation therapy (RT) with weekly cisplatin in Aug 2017, 6 cycles of carboplatin/5-fluorouracil/pembrolizumab from Apr 2021 to Aug 2021, and continuation of pembrolizumab from Sep 2021. Other medical history: Hypertension, hyperlipidemia, congestive heart failure, right knee repair, cardiac bypass surgery. Past medications: Cisplatin, Carboplatin, 5-Fluorouracil (fluorouracil) and Pembrolizumab. On 11 May 2022, the subject was enrolled in the study and was allocated to treatment Arm 1B. The subject experienced the following previous SAE: Refer case 9345912 for lung infection. On 30 Aug 2022, the subject experienced grade 4 pharyngeal stenosis. Due to the event, the subject was hospitalized. No relevant laboratory data was reported. Action taken with Bintrafusp Alfa (M7824) and HPV Vaccine in response to pharyngeal stenosis: Not Applicable Investigator's causality assessment:  Relationship with Bintrafusp Alfa (M7824) for the event pharyngeal stenosis: Suspected to be related. Relationship with HPV Vaccine for the event pharyngeal stenosis: Not Related.  Follow-up information received on 14-SEP-2022. This follow-up was considered significant Case received via MERCK . MERCK received case 14-SEP-2022 and subsequently forwarded to GSK on 22-SEP-2022 Summary of changes:It included the following new information: Pharyngeal stenosis outcome updated (previously not reported), Bintrafusp Alfa (M7824), HPV Vaccine and past drugs Cisplatin, Carboplatin, 5-Fluorouracil (fluorouracil) and Pembrolizumab.indication updated (previously: squamous cell carcinoma of oropharynx), additional medical history added, lab data added, subject weight updated (previously: 56 Kg), investigator details added and details about even added in the event description. LP Narrative:On 30 Aug 2022, the participant visited the clinical center with complaints of coughing up small blood clots along with intermittent difficulty in breathing and audible stridor. The subject reported significant difficulty getting in a full breath and being quite uncomfortable at night. The subject denied purulent sputum and had no more fevers. Vital signs included a body temperature of 36.1 C, HR of 79 bpm, BP of 142/68 mmHg, RR of 19 cpm, and oxygen saturation of 97%. The subject was obviously hoarse in inspiratory stridor and able to speak short sentences of eight to ten words. Laboratory evaluation revealed WBC count of 8.49 K/mcL, Hgb of 9.3 g/dL, HCT of 29.5%, PLT of 231 K/mcL, Na of 134 mmol/L, K of 5.1 mmol/L, Cr of 1.28 mg/dL, and BUN of 49 mg/dL. A CT neck was done which showed further enlargement of left neck mass with probable encasement of left vertebral artery, and increased nodularity of the pharyngeal mucosa, and CT of chest/abdomen/pelvis showed no evidence of lung, liver, or bone gross metastasis. The subject was evaluated by an ENT surgeon in clinic. A flexible nasopharyngolaryngoscopy was performed through right naris and showed severe crusting mixed with mucous and debris coating entire upper airway. The ENT surgeon recommended urgent admission for awake tracheostomy to secure the airway prior to performing biopsies of multiple mucosal friable lesions. The subject was admitted to the local hospital for tracheostomy placement. Further medical records have been requested from the site. Kindly refer the lab section for relevant laboratory data.  Case received via MERCK. MERCK received case 13Oct2022 and subsequently forwarded to GSK on 20Oct2022. Follow-up information received on 20Oct2022.  Summary of Changes: Follow-up information was received on 13 Oct 2022 from the investigator. It included the following new information: New event pharyngeal mucositis added, pharyngeal stenosis outcome updated (previously: not recovered) and cessation date added, HPV Vaccine frequency added, lab data added and details about events added in the event description.  Narrative information received from LP: MS200647 0073: 20-C-0104: Phase I/II Trial of HPV Vaccine PRGN-2009 Alone or in Combination with Bintrafusp alfa in Subjects with HPV Associated Cancers MA holder received this report from the above-mentioned investigator sponsored trial. This study case report from MS200647 0073 reported by an investigator in United States was initially received at Merck Healthcare KGaA on 02 Sep 2022. Investigator's causality assessment: Relationship with Bintrafusp Alfa (M7824) for all the events: Suspected to be related. Relationship with Hpv Vaccine for all the events: Not related. The investigator considered pharyngeal stenosis CTCAE v5 grade 4 as serious (hospitalization), unrelated to PRGN-2009 and related to M7824 confounded by disease progression mucositis. The investigator considered mucositis CTCAE v5 grade 4 as serious (hospitalization), unrelated to PRGN-2009 and related to M7824 confounded by disease (radiation recall). Per the principal investigator (PI), results of multiple biopsies from the pharyngeal walls indicated inflammation (mucositis) without cancer, so in retrospect, the cause of the pharyngeal stenosis was mucositis. This was confined to the prior mucosal radiation field and was considered as a radiation recall mucositis. Sponsor assessment: The sponsor assessed pharyngeal stenosis CTCAE v5 grade 4 as serious (hospitalization), unrelated and unexpected for PRGN-2009, and related and unexpected for M7824 confounded by radiographic and clinical evidence of mucositis (as noted by CT scan in AUG2022 - extensive post radiation prominence of parapharyngeal soft tissues that was mildly increasing within the region of the epiglottis; on 30AUG2022 - a flexible nasopharyngolaryngoscopy was performed and showed severe crusting mixed with mucous and debris coating his entire upper airway) causing upper airway obstruction. The sponsor assessed pharyngeal mucositis CTCAE v5 grade 4 as serious (hospitalization), unrelated and unexpected for PRGN-2009, and related and unexpected for M7824 confounded by radiation recall. Follow-up information was received on 14 Sep 2022 from the investigator. It included the following new information: Pharyngeal stenosis outcome updated (previously not reported), Bintrafusp Alfa (M7824), HPV Vaccine and past drugs Cisplatin, Carboplatin, 5-Fluorouracil (fluorouracil) and Pembrolizumab.indication updated (previously: squamous cell carcinoma of oropharynx), additional medical history added, lab data added, subject weight updated (previously: 56 Kg), investigator details added and details about even added in the event description.  Follow up information received on: 18-Oct-2022 Case received via Merck. Merck received case on 18 Oct 2022 and subsequently forwarded to GSK on 26 Oct 2022. Summary of changes: Rationale for assessing the event pharyngeal mucositis related to Bintrafusp Alfa (M7824) added in the event description.; Sender's Comments: Pharyngeal Mucositis (Pharyngeal Inflammation), Pharyngeal Stenosis (Pharyngeal Stenosis) in a 72 Years-old Male subject after administration of Bintrafusp Alfa (M7824) for the treatment of Head And Neck Cancer. Pharyngeal Stenosis, Pharyngeal Mucositis 28 days after the most recent and 111 days after the first administration. Company causality for serious events of Pharyngeal Stenosis, Pharyngeal Inflammation are assessed as not related to Bintrafusp Alfa (M7824). Alternative explanation for Pharyngeal Inflammation: underlying cancer disease, radiotherapy are risk factors; for Pharyngeal Stenosis: pharyngeal inflammation, underlying cancer disease with progression. Pharyngeal Inflammation (SUSAR), Pharyngeal Stenosis (SUSAR) are unexpected for Bintrafusp Alfa (M7824) as per Reference Safety Information (IB version 6).