Trial Outcomes & Findings for Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma (NCT NCT03370276)

Last Updated: 2025-12-08

Results Overview

Maximum Tolerated Dose (MTD).. The target Dose Limiting Toxicity (DLT) rate is \<25%. The MTD will be defined as the dose of cetuximab and nivolumab in which \<1 of 3 patients experience a DLT or \<2 of 6 patients experience a DLT with the next higher dose having at least 2 patients experiencing a DLT. The MTD is the highest dose at which at most 1 of 6 patients has a DLT. This study will utilize the Cancer Therapy Evaluation Program CTCAE version 4.1 for toxicity and event reporting. Dose-limiting toxicities will be observed until patients have completed Cycle 1 (4 weeks).

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

95 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2025-12-08

Participant Flow

Participants in lead-in were included in Cohort A for outcome measure data.

Participant milestones

Participant milestones
Measure	Phase I - Lead in Nivolumab and dose escalation of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2.	Phase II- Cohort A Patients who had progressed on at least one prior line of treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2.	Phase II - Cohort B Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2.
Overall Study STARTED	3	44	48
Overall Study COMPLETED	3	42	43
Overall Study NOT COMPLETED	0	2	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I - Lead in Nivolumab and dose escalation of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2.	Phase II- Cohort A Patients who had progressed on at least one prior line of treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2.	Phase II - Cohort B Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2.
Overall Study Death	0	2	5

Baseline Characteristics

Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I - Lead in n=3 Participants Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms.	Phase II - Cohort A n=44 Participants Patients who had progressed on at least one prior line of treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II - Cohort B n=48 Participants Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Total n=95 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants	0 Participants n=175 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=37 Participants	24 Participants n=37 Participants	32 Participants n=74 Participants	58 Participants n=175 Participants
Age, Categorical >=65 years	1 Participants n=37 Participants	20 Participants n=37 Participants	16 Participants n=74 Participants	37 Participants n=175 Participants
Sex: Female, Male Female	1 Participants n=37 Participants	7 Participants n=37 Participants	15 Participants n=74 Participants	23 Participants n=175 Participants
Sex: Female, Male Male	2 Participants n=37 Participants	37 Participants n=37 Participants	33 Participants n=74 Participants	72 Participants n=175 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=37 Participants	2 Participants n=37 Participants	2 Participants n=74 Participants	4 Participants n=175 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=37 Participants	41 Participants n=37 Participants	45 Participants n=74 Participants	89 Participants n=175 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	1 Participants n=37 Participants	1 Participants n=74 Participants	2 Participants n=175 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants	0 Participants n=175 Participants
Race (NIH/OMB) Asian	0 Participants n=37 Participants	1 Participants n=37 Participants	1 Participants n=74 Participants	2 Participants n=175 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants	0 Participants n=175 Participants
Race (NIH/OMB) Black or African American	0 Participants n=37 Participants	3 Participants n=37 Participants	3 Participants n=74 Participants	6 Participants n=175 Participants
Race (NIH/OMB) White	3 Participants n=37 Participants	39 Participants n=37 Participants	42 Participants n=74 Participants	84 Participants n=175 Participants
Race (NIH/OMB) More than one race	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants	0 Participants n=175 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	1 Participants n=37 Participants	2 Participants n=74 Participants	3 Participants n=175 Participants
Region of Enrollment United States	3 participants n=37 Participants	44 participants n=37 Participants	48 participants n=74 Participants	95 participants n=175 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Outcome measures

Outcome measures
Measure	Phase I - Lead in n=3 Participants Nivolumab and dose lead in of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II - Cohort B Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.
Phase I: Maximum Tolerated Dose	500 mg/m^2	—

PRIMARY outcome

Timeframe: Up to 24 months

Population: Evaluable participants

One year overall survival of concurrent cetuximab and nivolumab in patients with recurrent and/or metastatic HNSCC. OS: The length of time from the start of treatment until death by any cause.

Outcome measures

Outcome measures
Measure	Phase I - Lead in n=45 Participants Nivolumab and dose lead in of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II - Cohort B n=43 Participants Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.
Phase II: Overall Survival (OS)	11.4 months Interval 9.4 to 14.4	20.2 months Interval 15.7 to 24.7

SECONDARY outcome

Timeframe: Up to 48 months

Population: Participants evaluable for response

Complete Response (CR): The disappearance of all measurable lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameters of measureable lesions, taking as reference the baseline sum longest diameter. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s). Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 6 weeks.

Outcome measures

Outcome measures
Measure	Phase I - Lead in n=43 Participants Nivolumab and dose lead in of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II - Cohort B n=42 Participants Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.
Overall Response Rate (ORR)	22 percentage of participants responded	37 percentage of participants responded

SECONDARY outcome

Timeframe: at 12 months

Population: Evaluable participants

Progressive Disease (PD): At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).

Outcome measures

Outcome measures
Measure	Phase I - Lead in n=45 Participants Nivolumab and dose lead in of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II - Cohort B n=43 Participants Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.
Progression Free Survival (PFS)	3.35 months Interval 2.56 to 7.13	6.15 months Interval 3.06 to Not reached

SECONDARY outcome

Timeframe: Up to 48 months

Population: Evaluable participants

Related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) V4.1. An adverse event (AE) is defined as any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a patient in a clinical investigation who received a pharmaceutical product. A serious adverse event (SAE) is defined as any AE that results in death, is immediately life-threatening, results in persistent or significant disability/incapacity, requires or prolongs patient hospitalization, is a congenital anomaly/birth defect, or is to be deemed serious for any other reason if it is an important medical event when based on appropriate medical judgement that may jeopardize the patient and may require medical or surgical intervention to prevent one of the other outcomes listed in the above definitions.

Outcome measures

Outcome measures
Measure	Phase I - Lead in n=45 Participants Nivolumab and dose lead in of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II - Cohort B n=43 Participants Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.
Number of Study Treatment Related Adverse Events Grade 1	115 events	228 events
Number of Study Treatment Related Adverse Events Grade 2	105 events	142 events
Number of Study Treatment Related Adverse Events Grade 3	23 events	27 events
Number of Study Treatment Related Adverse Events Grade 4	1 events	1 events

Adverse Events

Phase I - Lead in

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase II- Cohort A

Serious events: 19 serious events

Other events: 43 other events

Deaths: 35 deaths

Phase II - Cohort B

Serious events: 19 serious events

Other events: 45 other events

Deaths: 33 deaths

Serious adverse events

Other adverse events

Additional Information

Christine Chung, MD

Moffitt Cancer Center

Phone: 813-745-5061

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The rights to publish the results of the study are vested in Moffitt. Subsite is free to publish any academic article, presentation or abstracts of the study results (including supporting data) twelve months after the conclusion or termination of the study provided that any such manuscript is first submitted to Moffitt sixty days prior to the proposed publication date.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Phase I - Lead in n=3 participants at risk Nivolumab and dose escalation of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II- Cohort A n=44 participants at risk Patients who had progressed on at least one prior line of treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II - Cohort B n=48 participants at risk Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.
Infections and infestations Sepsis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.2% 2/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Renal and urinary disorders Renal and urinary disorders -Other	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	11.4% 5/44 • Number of events 5 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
General disorders Death, NOS	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Surgical and medical procedures Surgical and medical procedures - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Gastrointestinal disorders Constipation	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified-Other	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	13.6% 6/44 • Number of events 6 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	6.2% 3/48 • Number of events 3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Cardiac disorders Atrial fibrilation	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
General disorders Flu like symptoms	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Infections and infestations Skin infection	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Reproductive system and breast disorders Pelvic pain	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Pharyngeal hemorrhage	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	11.4% 5/44 • Number of events 6 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	14.6% 7/48 • Number of events 11 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Injury, poisoning and procedural complications Tracheal hemorrhage	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Psychiatric disorders Confusion	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Infections and infestations Infections and Infestations - Other	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Nervous system disorders Lethargy	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Vascular disorders Thromboembolic event	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Injury, poisoning and procedural complications Fracture	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
General disorders Infusion related reaction	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Gastrointestinal disorders Colitis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Nervous system disorders Encephalopathy	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Nervous system disorders Tremor	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Nervous system disorders Dizziness	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Psychiatric disorders Hallucinations	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Infections and infestations Urinary tract infection	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.2% 2/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
General disorders Fever	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.2% 2/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Nervous system disorders Parasthesia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Gastrointestinal disorders Esophageal obstruction	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.

Other adverse events
Measure	Phase I - Lead in n=3 participants at risk Nivolumab and dose escalation of Cetuximab. Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m\^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m\^2; Nivolumab 240 mg. Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II- Cohort A n=44 participants at risk Patients who had progressed on at least one prior line of treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.	Phase II - Cohort B n=48 participants at risk Patients who have not had any prior treatment for their recurrent and/or metastatic HNSCC Participants were treated with Nivolumab and Cetuximab at recommended Phase II dose (RP2D). Nivolumab: Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms. Cetuximab: Cetuximab intravenously (IV) at 500 mg/m\^2 or 250 mg/m\^2 as outlined in the treatment arms.
Gastrointestinal disorders Ascites	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Gastrointestinal disorders Abdominal Pain	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	11.4% 5/44 • Number of events 6 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	8.3% 4/48 • Number of events 5 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Renal and urinary disorders Acute kidney injury	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	14.6% 7/48 • Number of events 11 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Investigations Alkaline phosphatase increased	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 6 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	14.6% 7/48 • Number of events 13 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Metabolism and nutrition disorders Alkalosis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Immune system disorders Allergic reaction	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Number of events 4 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	11.4% 5/44 • Number of events 6 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	29.2% 14/48 • Number of events 47 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Metabolism and nutrition disorders Anorexia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	18.2% 8/44 • Number of events 8 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	18.8% 9/48 • Number of events 10 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Psychiatric disorders Anxiety	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	8.3% 4/48 • Number of events 4 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	6.2% 3/48 • Number of events 4 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.2% 2/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	6.8% 3/44 • Number of events 5 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	10.4% 5/48 • Number of events 7 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	11.4% 5/44 • Number of events 6 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	22.9% 11/48 • Number of events 20 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Cardiac disorders Atrial fibrillation	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	9.1% 4/44 • Number of events 4 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	6.2% 3/48 • Number of events 3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Gastrointestinal disorders Bloating	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.2% 2/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Investigations Blood bilirubin increased	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Eye disorders Blurred vision	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	8.3% 4/48 • Number of events 4 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Infections and infestations Bronchial infection	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Cardiac disorders Chest pain - cardiac	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
General disorders Chills	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.2% 2/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Gastrointestinal disorders Colitis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.2% 2/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Psychiatric disorders Confusion	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	6.2% 3/48 • Number of events 4 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Eye disorders Conjunctivitis	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.2% 2/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Gastrointestinal disorders Constipation	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	36.4% 16/44 • Number of events 17 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	14.6% 7/48 • Number of events 7 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	15.9% 7/44 • Number of events 7 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	12.5% 6/48 • Number of events 7 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Investigations Creatinine increased	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	9.1% 4/44 • Number of events 4 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	6.2% 3/48 • Number of events 3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Psychiatric disorders Depression	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	4.5% 2/44 • Number of events 3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.1% 1/48 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	18.2% 8/44 • Number of events 16 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	25.0% 12/48 • Number of events 22 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	11.4% 5/44 • Number of events 5 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	14.6% 7/48 • Number of events 11 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Cardiac disorders Cardiac disorders - Other	66.7% 2/3 • Number of events 2 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/44 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.
Nervous system disorders Cognitive disturbance	0.00% 0/3 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	2.3% 1/44 • Number of events 1 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.	0.00% 0/48 • Adverse events collected from on study date to 30 days after completion of study therapy, approximately 2 years. All participants were followed for events, whether or not evaluable.