Cetuximab and Pembrolizumab in Treating Patients With Colorectal Cancer That is Metastatic or Cannot Be Removed by Surgery

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02713373
• Collaborator: National Cancer Institute (NCI) (NIH), Merck Sharp & Dohme LLC (Industry)
• Enrollment: 45
• Locations: 2
• Arm: 1
• Actual Duration (Months): 59.5
• Patients Per Site: 22.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of cetuximab when given together with pembrolizumab in treating patients with colorectal cancer that has spread from the primary site (place where it started) to other places in the body (metastatic) or that cannot be removed by surgery. Monoclonal antibodies, such as cetixumab and pembrolizumab, may block tumor growth in different ways by targeting certain cells.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Colorectal Carcinoma; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer	Biological: Cetuximab; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the objective response rate of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

2. To estimate the 6-month progression free survival (PFS) rate of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

3. To examine the adverse event profile of combining pembrolizumab and cetuximab.

SECONDARY OBJECTIVES:

1. To examine the PFS of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

2. To determine the objective response rate by immune-related response criteria (irRC) of patients with metastatic colorectal cancer.

3. To examine the overall survival of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

EXPLORATORY OBJECTIVES:

1. Identify tumor and peripheral blood biomarkers of response and/or resistance to the study treatment.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 120 minutes on day 1, 8, and 15 (as monotherapy for cycle 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression.

After completion of the study treatment, patients are followed up every 3 months for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase Ib/II Study of Cetuximab and Pembrolizumab in Metastatic Colorectal Cancer
• Actual Study Start Date: Aug 5, 2016
• Actual Primary Completion Date: Jul 28, 2020
• Actual Study Completion Date: Jul 20, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm I (cetuximab and pembrolizumab) Patients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression.

Biological: Cetuximab; Given IV; Other Names: Chimeric Anti-Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225 Erbitux IMC-C225 ; Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Pembrolizumab; Given IV; Other Names: Keytruda Lambrolizumab MK-3475 SCH 900475

Outcome Measures

Primary Outcome Measures

1. To Examine the Adverse Event Profile [up to 24 months]

   The frequency of toxicities will be tabulated by maximum grade by preferred term within a patient across all cycles.

2. Progression Free Survival (PFS), Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [At 6 months]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

3. Number of Participants With a Response, Evaluated According to RECIST 1.1 [Up to 2 years]

   Number of Participants with a Response, Evaluated According to RECIST 1.1 will be tabulated and will be compared to the null values using exact tests.

Secondary Outcome Measures

1. Objective Tumor Response Using Immune-related RECIST [up to 24 months]

   tumor response using immune-related RECIST (irRECIST) will be tabulated, summarized and reported.

2. Overall Survival (OS) [Up to death, withdrawal of consent, or the end of the study, whichever occurs first, assessed up to 2 years]

   Distributions of OS will be estimated using the Kaplan-Meier method.

3. Progression Free Survival (PFS) [At 6 months]

   PFS will be tested using an exact binomial test. Distributions of PFS will be estimated using the Kaplan-Meier method.

Other Outcome Measures

1. Change in Peripheral Blood Biomarkers Using ELISA (Enzyme Linked Immunosorbent Assay). [up to 12 weeks]

   Pre- and post-treatment levels and changes from pre- to post-treatment in biomarkers will be summarized overall and by response and 6-month PFS categories using summary statistics (e.g., mean or median, with dispersion measures, and using transformed values as appropriate). Depending on the number of responses, logistic regression models may be used to compare response rates across pre-treatment biomarker levels. Proportional hazards models may be used to examine progression-free survival and overall survival across biomarker levels.

2. Change in Tumor Biomarkers Using Immunohistochemistry [up to 12 weeks]

   Pre- and post-treatment levels and changes from pre- to post-treatment in biomarkers will be summarized overall and by response and 6-month PFS categories using summary statistics (e.g., mean or median, with dispersion measures, and using transformed values as appropriate). Depending on the number of responses, logistic regression models may be used to compare response rates across pre-treatment biomarker levels. Proportional hazards models may be used to examine progression-free survival and overall survival across biomarker levels.

3. Change in Tumor Immune Cell Populations Using Flow Cytometry [up to 12 weeks]

   Pre- and post-treatment levels and changes from pre- to post-treatment in biomarkers will be summarized overall and by response and 6-month PFS categories using summary statistics (e.g., mean or median, with dispersion measures, and using transformed values as appropriate). Depending on the number of responses, logistic regression models may be used to compare response rates across pre-treatment biomarker levels. Proportional hazards models may be used to examine progression-free survival and overall survival across biomarker levels.

4. Change in Peripheral Blood Biomarkers Using Flow Cytometry [up to 12 weeks]

   Pre and post treatment levels and changes form pre to post treatment in biomarkers will be summarized overall and by response and 6-month PFS categories using summary statistics (e.g., mean or median, with dispersion measures, and using transformed values as appropriate). Depending on the number of responses, logistic regression models may be used to compare response rates across pre-treatment biomarker levels. Proportional hazards models may be used to examine progression-free survival and overall survival across biomarker levels.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a pathologically confirmed diagnosis of colorectal cancer, which is metastatic or otherwise unresectable

• Have received at least 1 prior systemic therapy in the metastatic or unresectable disease setting; patients who have recurred within six months of adjuvant chemotherapy are not required to have received an additional line of chemotherapy

• Retrovirus-associated deoxyribonucleic acid (DNA) sequence (RAS) wild-type; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) testing must be completed, with full KRAS and neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) testing strongly advised; the presence of known mutations in KRAS or NRAS is exclusionary; primary tumor or metastatic tumor may be tested; (note: in the case of multiple genomic evaluations with conflicting results - e.g. KRAS mutant in one sample, but wild-type in another - the patient may be included as RAS wild-type, if clinically justified, after review with the principal investigator [PI])

• Appropriate for anti-EGFR therapy: Naive to anti-EGFR therapy (cetuximab or panitumumab) or a candidate for rechallenge by virtue of the following:

1. the investigator deems anti-EGFR retreatment with cetuximab to be a reasonable standard of care option AND

2. outcome of prior anti-EGFR therapy was not rapid progression (i.e. <= 3 months on therapy) AND

3. prior anti-EGFR therapy was administered > 6 months prior to the start of protocol therapy

• Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present

• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 30 days prior to initiation of treatment on day 1

• Hemoglobin >= 8 g/dL (performed within 14 days of treatment initiation)

• Absolute neutrophil count >= 1000/mm3 (performed within 14 days of treatment initiation)

• Platelet count >= 100,000/mm3 (performed within 14 days of treatment initiation)

• Serum creatinine =< 2 upper limit of normal (ULN) or, >= 15 mL/min for participants with creatinine levels > 2 ULN (performed within 14 days of treatment initiation)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 ULN or, =< 5 ULN for participants with liver metastases (performed within 14 days of treatment initiation)

• Female participants of childbearing potential are to have a negative serum pregnancy test

• Female participants of child-bearing potential must agree to use an acceptable method of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

• Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

• Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Participants who have had chemotherapy, targeted therapies, radiotherapy, or used an investigational device within 2 weeks prior to the first dose of treatment or those who have not recovered from adverse events (i.e., =< grade 1 or at baseline) due to agents administered more than 2 weeks earlier; note: participants with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment

• Has a known history of active TB (Bacillus Tuberculosis)

• Hypersensitivity to pembrolizumab or any of its excipients

• Prior severe infusion reaction to cetuximab

• Has a known additional malignancy that requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability

• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment

• Has known history of, or any evidence of active, non-infectious pneumonitis

• Uncontrolled clinically significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness, substance abuse disorders or social situations that would limit compliance with study requirements

• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

• Has a known history of human immunodeficiency virus (HIV or HIV 1/2 antibodies); testing not required

• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); testing not required

• Has received a live vaccine within 30 days of planned start of study therapy (note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and shingles are not allowed)

• Received an investigational agent within 30 days prior to starting study treatment

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

• Unwilling or unable to follow protocol requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
2	University Hospitals Seidman Cancer Center	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• Roswell Park Cancer Institute
• National Cancer Institute (NCI)
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Christos Fountzilas, Roswell Park Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 21, 2019

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT02713373
• Other Study ID Numbers: I 274515; NCI-2016-00228; I 274515; P30CA016056
• First Posted: Mar 18, 2016
• Last Update Posted: Aug 9, 2022
• Last Verified: Aug 1, 2022

• Additional relevant MeSH terms: Colorectal Neoplasms; Antineoplastic Agents, Immunological; Pembrolizumab; Cetuximab; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	Forty-five patients were enrolled in our study; one patient was not treated secondary to clinical progression during the screening period

Arm/Group Title	Arm I (Cetuximab and Pembrolizumab)
Arm/Group Description	Patients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression. Cetuximab: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Period Title: Overall Study
STARTED	44
COMPLETED	44
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm I (Cetuximab and Pembrolizumab)
Arm/Group Description	Patients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression. Cetuximab: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Overall Participants	44
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	25 56.8%
>=65 years	19 43.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (10.3)
Sex: Female, Male (Count of Participants)
Female	14 31.8%
Male	30 68.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 4.5%
White	42 95.5%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	To Examine the Adverse Event Profile
Description	The frequency of toxicities will be tabulated by maximum grade by preferred term within a patient across all cycles.
Time Frame	up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Cetuximab and Pembrolizumab)
Arm/Group Description	Patients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression. Cetuximab: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	44
Dry skin	21 47.7%
acneiform dermatitis	20 45.5%
fatigue	17 38.6%
hypomagnesemia	16 36.4%
rash	16 36.4%
diarrhea	12 27.3%
pruritus	12 27.3%
anorexia	10 22.7%

2. Primary Outcome

Title	Progression Free Survival (PFS), Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Cetuximab and Pembrolizumab)
Arm/Group Description	Patients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression. Cetuximab: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	44
Number (95% Confidence Interval) [percentage of PFS at 6 months]	31

3. Primary Outcome

Title	Number of Participants With a Response, Evaluated According to RECIST 1.1
Description	Number of Participants with a Response, Evaluated According to RECIST 1.1 will be tabulated and will be compared to the null values using exact tests.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Cetuximab and Pembrolizumab)
Arm/Group Description	Patients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression. Cetuximab: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	44
Count of Participants [Participants]	1 2.3%

4. Secondary Outcome

Title	Objective Tumor Response Using Immune-related RECIST
Description	tumor response using immune-related RECIST (irRECIST) will be tabulated, summarized and reported.
Time Frame	up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Distributions of OS will be estimated using the Kaplan-Meier method.
Time Frame	Up to death, withdrawal of consent, or the end of the study, whichever occurs first, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS will be tested using an exact binomial test. Distributions of PFS will be estimated using the Kaplan-Meier method.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Change in Peripheral Blood Biomarkers Using ELISA (Enzyme Linked Immunosorbent Assay).
Description	Pre- and post-treatment levels and changes from pre- to post-treatment in biomarkers will be summarized overall and by response and 6-month PFS categories using summary statistics (e.g., mean or median, with dispersion measures, and using transformed values as appropriate). Depending on the number of responses, logistic regression models may be used to compare response rates across pre-treatment biomarker levels. Proportional hazards models may be used to examine progression-free survival and overall survival across biomarker levels.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Change in Tumor Biomarkers Using Immunohistochemistry
Description	Pre- and post-treatment levels and changes from pre- to post-treatment in biomarkers will be summarized overall and by response and 6-month PFS categories using summary statistics (e.g., mean or median, with dispersion measures, and using transformed values as appropriate). Depending on the number of responses, logistic regression models may be used to compare response rates across pre-treatment biomarker levels. Proportional hazards models may be used to examine progression-free survival and overall survival across biomarker levels.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Change in Tumor Immune Cell Populations Using Flow Cytometry
Description	Pre- and post-treatment levels and changes from pre- to post-treatment in biomarkers will be summarized overall and by response and 6-month PFS categories using summary statistics (e.g., mean or median, with dispersion measures, and using transformed values as appropriate). Depending on the number of responses, logistic regression models may be used to compare response rates across pre-treatment biomarker levels. Proportional hazards models may be used to examine progression-free survival and overall survival across biomarker levels.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Change in Peripheral Blood Biomarkers Using Flow Cytometry
Description	Pre and post treatment levels and changes form pre to post treatment in biomarkers will be summarized overall and by response and 6-month PFS categories using summary statistics (e.g., mean or median, with dispersion measures, and using transformed values as appropriate). Depending on the number of responses, logistic regression models may be used to compare response rates across pre-treatment biomarker levels. Proportional hazards models may be used to examine progression-free survival and overall survival across biomarker levels.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	up to 24 months
Arm/Group Title	Arm I (Cetuximab and Pembrolizumab)
Arm/Group Description	Patients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression. Cetuximab: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
All Cause Mortality
	Arm I (Cetuximab and Pembrolizumab)
	Affected / at Risk (%)	# Events
Total	32/44 (72.7%)
Serious Adverse Events
	Arm I (Cetuximab and Pembrolizumab)
	Affected / at Risk (%)	# Events
Total	9/44 (20.5%)
Gastrointestinal disorders
Constipation	1/44 (2.3%)	1
Oesophageal perforation	1/44 (2.3%)	1
General disorders
Chest pain	1/44 (2.3%)	1
Pyrexia	1/44 (2.3%)	1
Infections and infestations
Abdominal infection	1/44 (2.3%)	1
Encephalitis	1/44 (2.3%)	1
Urinary tract infection	1/44 (2.3%)	2
Urosepsis	1/44 (2.3%)	1
Injury, poisoning and procedural complications
Fall	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/44 (2.3%)	1
Pneumonitis	3/44 (6.8%)	3
Other (Not Including Serious) Adverse Events
	Arm I (Cetuximab and Pembrolizumab)
	Affected / at Risk (%)	# Events
Total	44/44 (100%)
Blood and lymphatic system disorders
Anaemia	7/44 (15.9%)	26
Lymphopenia	2/44 (4.5%)	4
Cardiac disorders
Sinus tachycardia	2/44 (4.5%)	2
Tachycardia	1/44 (2.3%)	1
Ear and labyrinth disorders
Ear pain	2/44 (4.5%)	2
Endocrine disorders
Hyperthyroidism	1/44 (2.3%)	1
Hypothyroidism	3/44 (6.8%)	3
Eye disorders
Eye disorder	1/44 (2.3%)	1
Eye pruritus	1/44 (2.3%)	1
Papilloedema	1/44 (2.3%)	1
Vision blurred	3/44 (6.8%)	3
Visual impairment	1/44 (2.3%)	1
Gastrointestinal disorders
Abdominal distension	2/44 (4.5%)	2
Abdominal pain	4/44 (9.1%)	4
Abdominal pain upper	1/44 (2.3%)	1
Ascites	2/44 (4.5%)	3
Constipation	14/44 (31.8%)	22
Diarrhoea	15/44 (34.1%)	26
Dry mouth	4/44 (9.1%)	5
Dyspepsia	3/44 (6.8%)	3
Gastrooesophageal reflux disease	1/44 (2.3%)	1
Gingival pain	1/44 (2.3%)	1
Lip dry	1/44 (2.3%)	1
Mouth ulceration	1/44 (2.3%)	1
Nausea	10/44 (22.7%)	20
Oral pain	2/44 (4.5%)	2
Pancreatitis	1/44 (2.3%)	1
Proctalgia	1/44 (2.3%)	1
Rectal discharge	1/44 (2.3%)	1
Rectal haemorrhage	1/44 (2.3%)	1
Salivary duct inflammation	1/44 (2.3%)	1
Stomatitis	7/44 (15.9%)	8
Vomiting	9/44 (20.5%)	14
General disorders
Catheter site related reaction	1/44 (2.3%)	1
Chills	6/44 (13.6%)	6
Facial pain	1/44 (2.3%)	1
Fatigue	18/44 (40.9%)	31
Influenza like illness	1/44 (2.3%)	1
Infusion site reaction	1/44 (2.3%)	1
Mucosal inflammation	2/44 (4.5%)	2
Oedema	2/44 (4.5%)	2
Oedema peripheral	5/44 (11.4%)	5
Pain	3/44 (6.8%)	3
Pyrexia	7/44 (15.9%)	8
Tenderness	1/44 (2.3%)	1
Immune system disorders
Seasonal allergy	1/44 (2.3%)	1
Infections and infestations
Candida infection	1/44 (2.3%)	1
Conjunctivitis	1/44 (2.3%)	1
Infection	1/44 (2.3%)	1
Lung infection	1/44 (2.3%)	1
Paronychia	2/44 (4.5%)	3
Pneumonia	1/44 (2.3%)	1
Rash pustular	1/44 (2.3%)	1
Upper respiratory tract infection	1/44 (2.3%)	3
Urinary tract infection	3/44 (6.8%)	3
Injury, poisoning and procedural complications
Infusion related reaction	9/44 (20.5%)	10
Procedural pain	1/44 (2.3%)	1
Sunburn	1/44 (2.3%)	1
Investigations
Alanine aminotransferase increased	4/44 (9.1%)	14
Aspartate aminotransferase increased	5/44 (11.4%)	8
Blood alkaline phosphatase	1/44 (2.3%)	1
Blood alkaline phosphatase increased	4/44 (9.1%)	6
Blood bilirubin increased	2/44 (4.5%)	3
Blood creatinine increased	3/44 (6.8%)	23
Blood magnesium decreased	2/44 (4.5%)	2
Carbon dioxide decreased	1/44 (2.3%)	1
International normalised ratio	1/44 (2.3%)	1
International normalised ratio increased	1/44 (2.3%)	3
Lymphocyte count decreased	4/44 (9.1%)	11
Lymphocyte count increased	1/44 (2.3%)	1
Platelet count decreased	1/44 (2.3%)	2
Transaminases increased	1/44 (2.3%)	1
Troponin increased	1/44 (2.3%)	1
Weight decreased	2/44 (4.5%)	2
Weight increased	1/44 (2.3%)	3
White blood cell count decreased	1/44 (2.3%)	4
Metabolism and nutrition disorders
Decreased appetite	10/44 (22.7%)	17
Hyperglycaemia	1/44 (2.3%)	1
Hypermagnesaemia	1/44 (2.3%)	1
Hypernatraemia	1/44 (2.3%)	1
Hypoalbuminaemia	1/44 (2.3%)	1
Hypocalcaemia	4/44 (9.1%)	12
Hypokalaemia	6/44 (13.6%)	22
Hypomagnesaemia	17/44 (38.6%)	54
Hyponatraemia	3/44 (6.8%)	12
Hypophosphataemia	1/44 (2.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	4/44 (9.1%)	6
Back pain	6/44 (13.6%)	10
Bone pain	1/44 (2.3%)	1
Flank pain	2/44 (4.5%)	2
Muscle spasms	3/44 (6.8%)	4
Muscular weakness	1/44 (2.3%)	3
Musculoskeletal chest pain	1/44 (2.3%)	1
Musculoskeletal pain	3/44 (6.8%)	3
Myalgia	1/44 (2.3%)	1
Pain in extremity	2/44 (4.5%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/44 (2.3%)	1
Nervous system disorders
Dizziness	5/44 (11.4%)	5
Drooling	1/44 (2.3%)	1
Headache	7/44 (15.9%)	7
Hyperaesthesia	1/44 (2.3%)	1
Neuropathy peripheral	1/44 (2.3%)	1
Peripheral sensory neuropathy	3/44 (6.8%)	3
Sciatica	1/44 (2.3%)	2
Taste disorder	3/44 (6.8%)	3
Psychiatric disorders
Agitation	1/44 (2.3%)	1
Depression	2/44 (4.5%)	2
Insomnia	8/44 (18.2%)	12
Renal and urinary disorders
Nephrolithiasis	1/44 (2.3%)	1
Proteinuria	1/44 (2.3%)	1
Urinary retention	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	11/44 (25%)	19
Dyspnoea	10/44 (22.7%)	17
Epistaxis	1/44 (2.3%)	1
Hypoxia	1/44 (2.3%)	1
Nasal congestion	3/44 (6.8%)	3
Nasal dryness	1/44 (2.3%)	1
Paranasal sinus discomfort	1/44 (2.3%)	1
Pneumonitis	1/44 (2.3%)	2
Productive cough	3/44 (6.8%)	5
Rhinitis allergic	1/44 (2.3%)	1
Skin and subcutaneous tissue disorders
Dermatitis	1/44 (2.3%)	1
Dermatitis acneiform	20/44 (45.5%)	32
Dermatitis bullous	1/44 (2.3%)	2
Drug eruption	1/44 (2.3%)	1
Dry skin	21/44 (47.7%)	26
Erythema	2/44 (4.5%)	2
Hair growth abnormal	3/44 (6.8%)	3
Hirsutism	1/44 (2.3%)	1
Hyperhidrosis	1/44 (2.3%)	1
Hypertrichosis	1/44 (2.3%)	1
Nail disorder	7/44 (15.9%)	7
Nail growth abnormal	1/44 (2.3%)	1
Night sweats	2/44 (4.5%)	2
Onychoclasis	3/44 (6.8%)	3
Photosensitivity reaction	1/44 (2.3%)	1
Pruritus	13/44 (29.5%)	14
Rash	16/44 (36.4%)	24
Rash generalised	1/44 (2.3%)	1
Rash maculo-papular	2/44 (4.5%)	3
Skin fissures	3/44 (6.8%)	4
Skin hyperpigmentation	1/44 (2.3%)	1
Urticaria	1/44 (2.3%)	1
Vascular disorders
Flushing	1/44 (2.3%)	1
Hot flush	1/44 (2.3%)	1
Hypertension	3/44 (6.8%)	46

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.