Study to Assess the Efficacy and Safety of Nivolumab in C... | NCT04282109

ID	Type	Description	Link
2019-002922-60	EudraCT Number

Name	Class
Bristol-Myers Squibb	INDUSTRY
Apices Soluciones S.L.	INDUSTRY

Label	Type	Description	Intervention Names
Arm 1	Experimental	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab)	Drug: Nivolumab + Paclitaxel
Arm 2	Active Comparator	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab)	Drug: Cetuximab + Paclitaxel

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab + Paclitaxel	Drug	Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Measure	Description	Time Frame
Two Years Overall Survival (OS)	OS is defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive.	2 years

Measure	Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.	Up to 45 months
Overall Response Rate (ORR)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care.
Histologically confirmed HNSCC (oral cavity, oropharynx, hypopharynx, larynx) not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
Patients not previously treated for recurrent/metastatic disease.
Radiographically measurable disease as defined by RECIST version 1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression according to RECIST version 1.1.
Patients unable for cisplatin-based chemotherapy, defined "unable" by:
1. Karnofsky 70% or
2. Karnofsky 80-100% and amenable to chemotherapy, but:
i. Impaired renal function, creatinine clearance >30 mL/min and <80 mL/min GFR could be assessed by direct measurement (EDTA or creatinine clearance) if available or by calculation from serum or plasma creatinine (see annex 5), or

ii. grade ≥2 hearing loss, according to the NCI CTCAE v 5.0, or

iii. Class III heart failure according to the New York Heart Association (annex 9), or

iv. History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds or

v. Prior dose of cisplatin ≥225 mg/m² for locally advanced disease (a patient who received prior RT + 3 cycles of cisplatin 100 mg/m2 or 3 cycles induction TPF (with cisplatin ≥75/m2) for locally advanced primary HN cancer can be included), or

vi. Disease progression or relapse during or within 6 months of receiving platinum-based therapy administered as neoadjuvant, adjuvant therapy or as concomitant chemotherapy with radiotherapy and have received at least 200 mg/m2 of cisplatin.
Male or female patients aged ≥18 years. Patients aged ≥70 years old can only be included with a G8 (Geriatric 8) health status screening score ≥ 14.
Clinical laboratory values as specified below within 28 days before the first dose of study drug:
1. Total bilirubin must be ≤2 × the upper limit of normal (ULN).
2. Magnesium ≥ lower limit of normal.
3. Calcium ≥ lower limit of normal.
4. ALT and AST must be ≤3 × ULN unless liver metastases are present, in which case they must be ≤5x ULN.
5. Hemoglobin must be ≥9 g/dL, absolute neutrophil count (ANC) must be ≥1.500/µL, WBC must be ≥2.000/µL and platelet count must be ≥100.000/µL.
Subjects who have received radiation as primary therapy are eligible if radiation therapy treatment was completed > 4 weeks prior to inclusion.
Documentation of PD-L1 status by IHC performed by the central lab at randomization. A pre-treatment tumor tissue sample should be sent. A newly obtained biopsy (within 6 months prior to start of study treatment) is preferred but an archival sample is acceptable, if several tumor samples are available, testing should be performed on the most recently obtained tumor sample.
Documentation of HPV p16 status (OPC) is required for HNSCC tumor of the oropharynx. For subjects with oropharyngeal cancer, sites are defined in annex 8. HPV status of tumor tissue has to be locally determined at screening by any of the following methods: p16 IHC, in situ hybridization, or polymerase chain reaction based assay. If HPV status by p16 IHC is positive result confirmation by PCR is mandatory.

Exclusion Criteria:

Male or female patients aged <18 years. Patients aged ≥ 70 years old should not be included with a G8 (Geriatric 8) health status screening score < 14.
Karnofsky <70%.
Patients that meets more than one of the following criteria:
1. Karnofsky 70%,
2. Impaired renal function, creatinine clearance >30 mL/min and <80 mL/min GFR could be assessed by direct measurement (EDTA or creatinine clearance) if available or by calculation from serum or plasma creatinine (see annex 5),
3. Class III heart failure according to the New York Heart Association (annex 9).
Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy except for alopecia, vitiligo, hear loss and the laboratory values defined in the inclusion criteria.
Histologically confirmed recurrent or metastatic squamous cell carcinoma of unknown primary, of the nasopharynx or non-squamous histologies (eg, mucosal melanoma).
Active brain metastases or leptomeningeal metastases.
Carcinomatous meningitis.
Active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
Diagnosis of immunodeficiency or any condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment.
History of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Patients with a history of interstitial lung disease cannot be included if they have symptomatic ILD (Grade 3-4) and/or poor lung function.
Prior therapy with experimental antitumor vaccines; any T-cell co-stimulation agents or inhibitors of checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody; or other agents specifically targeting T cells are prohibited.
Any serious medical or psychiatric illness, including drug or alcohol abuse, that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Life-threatening illness unrelated to cancer.
Female patients who are lactating and breast-feeding or a positive serum pregnancy test during the screening period.
Systemic anticancer treatment or radiotherapy less than 4 weeks or 5 half-lives, whichever is longer, before the first dose of study treatment or not recovered from acute toxic effects from prior chemotherapy and radiotherapy.
Prior treatment with investigational agents ≤21 days (≤4 weeks for monoclonal antibodies with evidence of PD) or ≤5 their half-lives (whichever is shorter) before the first dose of study treatment. A minimum of 10 days should elapse from prior therapy to initiating protocol therapy.
Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery.
Systemic infection requiring IV antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
Known human immunodeficiency virus (HIV) positive (testing not required), or known acquired immunodeficiency syndrome (AIDS).
Patients with positive test for hepatitis B virus or hepatitis C virus indicating presence of virus, eg, Hepatitis B surface antigen (HBsAg) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).
Active secondary malignancy that requires treatment. Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period
Any clinically significant co-morbidities, such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
Patients with history of hypersensitivity reactions to study drugs (nivolumab, cetuximab or paclitaxel) or any of their excipients.
Symptomatic peripheral neuropathy of Grade ≥ 2 based on the CTCAE v5.0
Pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event ≤ 8 weeks prior to starting the study treatment.
History of severe skin disorder that in the opinion of the investigator may interfere with study conduct.

Name	Affiliation	Role
Ricard Mesia, MD	Hospital Universitari Germans Trias i Pujol de Badalona	Principal Investigator
Lara Iglesias, MD	Hospital Universitario 12 de Octubre	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Hospital Universitario Marqués de Valdecilla		Santander	Cantabria	39008	Spain
Hospital Universitario Donostia- Donostia Unibertsitate Ospitalea

ID	Title	Description
FG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 19, 2022	Feb 25, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Two Years Overall Survival (OS)

OS is defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive.

Posted

Number

95% Confidence Interval

percentage of participants

2 years

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Units	Counts
Participants	OG00093 OG00148

Title

Denominators

Categories

Title	Measurements
	OG00024.7(15.9 to 33.5) OG00113.4(3.6 to 23.2)

Secondary

Progression Free Survival (PFS)

PFS is defined as the time from randomization to the date of first documented disease progression, as assessed by the investigator using RECIST 1.1 criteria, or death due to any cause, whichever occurs first.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Overall Response Rate (ORR)

ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Disease Control Rate (DCR)

Disease control rate (DCR) is defined as the number of subjects with a best overall response (BOR) of a complete response (CR), partial response (PR) or stable disease (SD) divided by the number of randomized subjects for each treatment group.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Duration of Response (DoR)

Duration of Response (DoR) is defined as the time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first.

Posted

Median

95% Confidence Interval

month

Up to 45 months

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

6-months Progression-free Survival Rate

Probability of progression at 6 months.

Posted

Number

95% Confidence Interval

percentage of participants

6 months

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Overall Survival in Patients ≥ 70 Years.

OS is defined as the time between the date of randomization and the date of death.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Progression Free Survival in Patients ≥ 70 Years.

Posted

Median

95% Confidence Interval

month

Up to 45 months

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Overall Response Rate in Patients ≥ 70 Years.

ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.

Patients ≥ 70 years.

Posted

Number

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Overall Survival Based on PDL1 Expression (CPS).

OS is defined as the time between the date of randomization and the date of death.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	Arm 1 - CPS <1	NIVOTAX - CPS <1
OG001	Arm 1 - CPS >=1	NIVOTAX - CPS >=1
OG002	Arm 2 - CPS <1	ERBITAX - CPS <1
OG003	Arm 2 - CPS >=1	ERBITAX - CPS >=1

Units	Counts
Participants	OG000

Secondary

Progression Free Survival Based on PDL1 Expression (CPS).

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	Arm 1 - CPS <1	NIVOTAX - CPS <1
OG001	Arm 1 - CPS >=1	NIVOTAX - CPS >=1
OG002	Arm 2 - CPS <1	ERBITAX - CPS <1
OG003	Arm 2 - CPS >=1	ERBITAX - CPS >=1

Units	Counts
Participants

Secondary

Overall Response Rate Based on PDL1 Expression (CPS).

ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.

Posted

Number

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Arm 1 - CPS <1	NIVOTAX - CPS <1
OG001	Arm 1 - CPS >=1	NIVOTAX - CPS >=1
OG002	Arm 2 - CPS <1	ERBITAX - CPS <1
OG003	Arm 2 - CPS >=1	ERBITAX - CPS >=1

Units	Counts
Participants

Secondary

Overall Survival Based on Cisplatin Ineligibility.

OS is defined as the time between the date of randomization and the date of death.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	Arm 1 - Group 1	NIVOTAX - Group 1 Platinum resistant population: - Patients who have experienced disease progression or relapse during or within 6 months of receiving platinum-based therapy administered as neoadjuvant, adjuvant therapy or as concomitant chemotherapy with radiotherapy and have received at least 200 mg/m2 of cisplatin.
OG001	Arm 1 - Group 2	NIVOTAX - Group 2 Platinum sensitive but unable for cisplatin based therapy according to one of these criteria: Karnofsky grade 70% or Impaired renal function, creatinine clearance >30 mL/min and <80 mL/min GFR could be assessed by direct measurement (EDTA or creatinine clearance) if available or by calculation from serum or plasma creatinine, or Class III heart failure according to the New York Heart Association, or Grade ≥2 hearing loss, according to the NCI CTCAE v 5.0, or History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds.
OG002	Arm 1 - Group 3	NIVOTAX - Group 3 Platinum sensitive but prior dose of cisplatin ≥225 mg/m² for locally advanced disease (one third of the patients - 47 patients) (a patient who received prior RT + 3 cycles of cisplatin 100 mg/m2 or 3 cycles induction TPF (with cisplatin ≥75/m2) for locally advanced primary HN cancer). The interval from the last cycle of cisplatin and the start of first line treatment for R/M disease is >6 months.

Secondary

Progression Free Survival Based on Cisplatin Ineligibility.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	Arm 1 - Group 1	NIVOTAX - Group 1 Platinum resistant population: - Patients who have experienced disease progression or relapse during or within 6 months of receiving platinum-based therapy administered as neoadjuvant, adjuvant therapy or as concomitant chemotherapy with radiotherapy and have received at least 200 mg/m2 of cisplatin.
OG001	Arm 1 - Group 2	NIVOTAX - Group 2 Platinum sensitive but unable for cisplatin based therapy according to one of these criteria: Karnofsky grade 70% or Impaired renal function, creatinine clearance >30 mL/min and <80 mL/min GFR could be assessed by direct measurement (EDTA or creatinine clearance) if available or by calculation from serum or plasma creatinine, or Class III heart failure according to the New York Heart Association, or Grade ≥2 hearing loss, according to the NCI CTCAE v 5.0, or History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds.
OG002	Arm 1 - Group 3

Secondary

Overall Response Rate Based on Cisplatin Ineligibility.

ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.

Posted

Number

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Arm 1 - Group 1	NIVOTAX - Group 1 Platinum resistant population: - Patients who have experienced disease progression or relapse during or within 6 months of receiving platinum-based therapy administered as neoadjuvant, adjuvant therapy or as concomitant chemotherapy with radiotherapy and have received at least 200 mg/m2 of cisplatin.
OG001	Arm 1 - Group 2	NIVOTAX - Group 2 Platinum sensitive but unable for cisplatin based therapy according to one of these criteria: Karnofsky grade 70% or Impaired renal function, creatinine clearance >30 mL/min and <80 mL/min GFR could be assessed by direct measurement (EDTA or creatinine clearance) if available or by calculation from serum or plasma creatinine, or Class III heart failure according to the New York Heart Association, or Grade ≥2 hearing loss, according to the NCI CTCAE v 5.0, or History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds.
OG002	Arm 1 - Group 3

Secondary

Overall Survival Based on Karnofsky.

OS is defined as the time between the date of randomization and the date of death.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	Arm 1 - Karnofsky-PS 70%	NIVOTAX - Karnofsky-PS 70%
OG001	Arm 1 - Karnofsky-PS 80-100%	NIVOTAX - Karnofsky-PS 80-100%
OG002	Arm 2 - Karnofsky-PS 70%	ERBITAX - Karnofsky-PS 70%
OG003	Arm 2 - Karnofsky-PS 80-100%	ERBITAX - Karnofsky-PS 80-100%

Units	Counts
Participants

Secondary

Progression Free Survival Based on Karnofsky.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	Arm 1 - Karnofsky-PS 70%	NIVOTAX - Karnofsky-PS 70%
OG001	Arm 1 - Karnofsky-PS 80-100%	NIVOTAX - Karnofsky-PS 80-100%
OG002	Arm 2 - Karnofsky-PS 70%	ERBITAX - Karnofsky-PS 70%
OG003	Arm 2 - Karnofsky-PS 80-100%	ERBITAX - Karnofsky-PS 80-100%

Units	Counts
Participants

Secondary

Overall Response Rate Based on Karnofsky.

ORR is defined as the number of subjects with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized subjects for each treatment group.

Posted

Number

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Arm 1 - Karnofsky-PS 70%	NIVOTAX - Karnofsky-PS 70%
OG001	Arm 1 - Karnofsky-PS 80-100%	NIVOTAX - Karnofsky-PS 80-100%
OG002	Arm 2 - Karnofsky-PS 70%	ERBITAX - Karnofsky-PS 70%
OG003	Arm 2 - Karnofsky-PS 80-100%	ERBITAX - Karnofsky-PS 80-100%

Units	Counts
Participants

Secondary

Percentage of Patients With AEs

Percentage of patients with AEs in relation with total number of treated patients

Posted

Number

percentage of participants

2 years

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Percentage of Patients With Grade 3 and Grade 4 AEs

Percentage of patients with Grade 3 and Grade 4 AEs in relation with total number of treated patients

Patients with at least one adverse event G≥3 during study

Posted

Number

percentage of participants

2 years

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Percentage of Patients With SAEs

Percentage of patients with SAEs in relation with total number of treated patients

Posted

Number

percentage of participants

Up to 45 months

ID	Title	Description
OG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
OG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.

Secondary

Percentage of Patients Who Discontinued Due to AEs

Percentage of patients who discontinued due to AEs in relation with total number of treated patients

Posted

Number

percentage of participants

Up to 2 years

ID	Title	Description
OG000	Arm 1 - Combination Phase	NIVOTAX - Combination phase
OG001	Arm 1 - Monotherapy Phase	NIVOTAX - Monotherapy phase
OG002	Arm 2 - Combination Phase	ERBITAX - Combination phase
OG003	Arm 2 - Monotherapy Phase	ERBITAX - Monotherapy phase

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angiosarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Colorectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected93 at risk EG0010 events0 affected48 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected93 at risk EG0011 events1 affected48 at risk
Gastrostomy	Surgical and medical procedures	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Hernia repair	Surgical and medical procedures	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Death	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Disease progression	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Face oedema	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Impaired healing	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Mucosal inflammation	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected48 at risk
Hypersensitivity	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Pharyngeal haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected93 at risk EG0011 events1 affected48 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected93 at risk EG0011 events1 affected48 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected93 at risk EG0010 events0 affected48 at risk
Product administration error	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected48 at risk
Product dispensing error	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected93 at risk EG0010 events0 affected48 at risk
Radiation proctitis	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Cardiac failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Myocarditis	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Diplopia	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0011 events1 affected48 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0008 events7 affected93 at risk EG0012 events1 affected48 at risk
Gastritis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Submaxillary gland enlargement	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0012 events2 affected48 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected93 at risk EG0010 events0 affected48 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Renal failure	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Hypercalcaemia of malignancy	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Hip fracture	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Appendicitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Cholecystitis infective	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
COVID-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Device related bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Device related infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Empyema	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Infected fistula	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Infected skin ulcer	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Intervertebral discitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Klebsiella infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0009 events9 affected93 at risk EG0012 events2 affected48 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected93 at risk EG0010 events0 affected48 at risk
Post procedural infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected93 at risk EG0016 events6 affected48 at risk
Sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected93 at risk EG0012 events1 affected48 at risk
Septic shock	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Stenotrophomonas sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Stoma site cellulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk
Urinary tract infection pseudomonal	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0011 events1 affected48 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0010 events0 affected48 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0006 events5 affected93 at risk EG0012 events1 affected48 at risk
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0007 events5 affected93 at risk EG0011 events1 affected48 at risk
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG000166 events57 affected93 at risk EG00161 events29 affected48 at risk
Crepitations	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0015 events4 affected48 at risk
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG00022 events11 affected93 at risk EG0017 events3 affected48 at risk
Mucosal inflammation	General disorders	MedDRA 27.0	Systematic Assessment	EG00032 events15 affected93 at risk EG00142 events16 affected48 at risk
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG0006 events5 affected93 at risk EG0014 events3 affected48 at risk
Pain	General disorders	MedDRA 27.0	Systematic Assessment	EG00010 events9 affected93 at risk EG0018 events4 affected48 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG00022 events15 affected93 at risk EG00110 events6 affected48 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00015 events10 affected93 at risk EG0014 events3 affected48 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0016 events4 affected48 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00016 events11 affected93 at risk EG0012 events2 affected48 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00012 events10 affected93 at risk EG0015 events4 affected48 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0007 events7 affected93 at risk EG0012 events2 affected48 at risk
Anxiety	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected93 at risk EG0011 events1 affected48 at risk
Insomnia	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0007 events7 affected93 at risk EG0010 events0 affected48 at risk
Amylase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00010 events5 affected93 at risk EG0011 events1 affected48 at risk
Lipase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00015 events6 affected93 at risk EG0013 events2 affected48 at risk
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0009 events4 affected93 at risk EG0016 events4 affected48 at risk
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0008 events6 affected93 at risk EG0014 events4 affected48 at risk
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00010 events8 affected93 at risk EG0014 events2 affected48 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00014 events10 affected93 at risk EG00115 events7 affected48 at risk
Neurotoxicity	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00038 events22 affected93 at risk EG00116 events10 affected48 at risk
Paraesthesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0008 events6 affected93 at risk EG0015 events5 affected48 at risk
Syncope	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0013 events3 affected48 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG00086 events41 affected93 at risk EG00147 events19 affected48 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG00037 events17 affected93 at risk EG00118 events11 affected48 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected93 at risk EG0014 events3 affected48 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected93 at risk EG0015 events3 affected48 at risk
Cheilitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected93 at risk EG0017 events4 affected48 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00029 events23 affected93 at risk EG00116 events14 affected48 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00040 events26 affected93 at risk EG00124 events14 affected48 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0007 events5 affected93 at risk EG0010 events0 affected48 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00019 events16 affected93 at risk EG0018 events8 affected48 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00015 events13 affected93 at risk EG0016 events6 affected48 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00011 events9 affected93 at risk EG0017 events5 affected48 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00011 events9 affected93 at risk EG0017 events6 affected48 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00036 events26 affected93 at risk EG0018 events6 affected48 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected93 at risk EG0013 events3 affected48 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected93 at risk EG00117 events8 affected48 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected93 at risk EG0019 events7 affected48 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected93 at risk EG0011 events1 affected48 at risk
Hypertrichosis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0013 events3 affected48 at risk
Nail toxicity	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0013 events3 affected48 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00018 events11 affected93 at risk EG0018 events6 affected48 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00013 events10 affected93 at risk EG00158 events25 affected48 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0019 events5 affected48 at risk
Skin toxicity	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected93 at risk EG00114 events9 affected48 at risk
Hypothyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG00017 events13 affected93 at risk EG0014 events3 affected48 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00020 events12 affected93 at risk EG0015 events4 affected48 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected93 at risk EG0013 events2 affected48 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00013 events11 affected93 at risk EG0013 events3 affected48 at risk
Conjunctivitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected93 at risk EG0017 events6 affected48 at risk
COVID-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected93 at risk EG0013 events3 affected48 at risk
Oral candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0007 events5 affected93 at risk EG0012 events2 affected48 at risk
Paronychia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected93 at risk EG0018 events5 affected48 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0006 events5 affected93 at risk EG0010 events0 affected48 at risk
Respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00024 events16 affected93 at risk EG00111 events7 affected48 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0009 events9 affected93 at risk EG0016 events4 affected48 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00035 events17 affected93 at risk EG00117 events14 affected48 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0008 events7 affected93 at risk EG0014 events3 affected48 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0008 events6 affected93 at risk EG00135 events15 affected48 at risk

ID	Term
D000077195	Squamous Cell Carcinoma of Head and Neck
D006258	Head and Neck Neoplasms
D002294	Carcinoma, Squamous Cell

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

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description
BG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab). Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
BG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab). Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1	NIVOTAX (nivolumab + paclitaxel, follow by maintenance with nivolumab) Nivolumab + Paclitaxel: Combination treatment: Nivolumab 240 mg will be administered via IV infusion every 2 weeks. Paclitaxel 80mg/m2 will be administered via IV infusion weekly. After 12 weeks from the start of the combined treatment paclitaxel will be stopped. Maintenance treatment with nivolumab 480 mg every 4 weeks will start two weeks after the last administration of nivolumab 240 mg. Once nivolumab is administered at 480 mg, paclitaxel can no longer be administered. Nivolumab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.	79	93	53	93	93	93
EG001	Arm 2	ERBITAX (cetuximab + paclitaxel, follow by maintenance with cetuximab) Cetuximab + Paclitaxel: Combination treatment: Cetuximab 250 mg/m2 (first dose of 400 mg/m2) administered via IV infusion weekly plus weekly paclitaxel (80 mg/m2) administered via IV infusion. After 12 weeks from the start of the combined treatment paclitaxel will be stopped and weekly cetuximab will be continued alone until disease progression, unacceptable toxicity or withdrawal of consent up to a maximum of 24 months.	43	48	26	48	48	48