Conatumumab/Panitumumab Combination Metastatic Colorectal Cancer Study

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00630786
• Collaborator: (none)
• Enrollment: 53
• Arm: 1
• Duration (Months): 34

Study Details

Study Description

Brief Summary

This is an exploratory phase 1b/2, global, multicenter, single-arm, 2-part (phase 1b and 2) study of conatumumab in combination with panitumumab in patients with Metastatic Colorectal Cancer.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer; Colorectal Cancer; Rectal Cancer; Metastatic Colorectal Cancer; Oncology	Drug: Panitumumab; Drug: Conatumumab	Phase 1/Phase 2

Detailed Description

This is an exploratory phase 1b/2, global, multicenter, single-arm, 2-part (phase 1b and 2) study of conatumumab in combination with panitumumab in patients with Metastatic Colorectal Cancer.

The objective for Part 1 is to identify a tolerable dose of conatumumab in combination with panitumumab based on the incidence of dose-limiting toxicities in patients with Metastatic Colorectal Cancer.

The objective for Part 2 is to evaluate the objective response rate stratified by Kirsten Rat Sarcoma Virus Oncogene (KRAS) status (wild-type versus mutant) in patients with Metastatic Colorectal Cancer treated with the combination of panitumumab and conatumumab (tolerable dose identified in part 1).

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2 Trial of AMG 655 in Combination With Panitumumab in Subjects With Metastatic Colorectal Cancer
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panitumumab plus conatumumab Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Drug: Panitumumab; Administered by intravenous infusion; Other Names: Vectibix® ; Drug: Conatumumab; Administered by intravenous infusion; Other Names: AMG 655

Outcome Measures

Primary Outcome Measures

1. Part 1: Number of Participants With Dose-limiting Toxicities [4 weeks]

   A dose-limiting toxicity (DLT) was defined as any grade 3 or 4 conatumumab-related or combination (panitumumab and conatumumab)-related adverse event, or grade 3 or 4 laboratory abnormality that occurred during the first 4 weeks (28 days) of treatment with panitumumab and conatumumab. Anemia and lymphopenia were not considered DLTs. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to grade all adverse events and toxicities.

2. Number of Participants With an Objective Response [Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).]

   An overall objective response of either a confirmed complete response or partial response, where the overall objective response was equivalent to the best overall response recorded for each participant from enrollment until disease progression or recurrence. Tumor response was assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Responses were confirmed no less than 4 weeks after the criteria for response were first met. Complete response defined as the disappearance of all target and non-target lesions and no new lesions. Partial response defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions.

Secondary Outcome Measures

1. Progression-free Survival [Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).]

   Kaplan-Meier estimate of the median time from enrollment to death from any cause or disease progression. Progressive disease is defined as at least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started, or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.

2. Overall Survival [Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).]

   Kaplan-Meier estimate of time from enrollment to death from any cause

3. Number of Participants With Disease Control [Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).]

   Disease control defined as participants with an overall objective response of complete response (CR), partial response (PR), or stable disease during the treatment period, assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST). Responses were confirmed no less than 4 weeks after the criteria for response were first met. CR defined as the disappearance of all target and non-target lesions and no new lesions. PR defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the nadir LD since the treatment started.

4. Time to Response [Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).]

   The interval in days from the first dose of study therapy to the date of first confirmed objective response. Calculated only for participants with an objective response.

5. Duation of Response [Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).]

   The interval in days from the first confirmed objective response to disease progression per the modified RECIST criteria or death. Calculated only for participants with an objective response.

6. Number of Participants With Anti-therapeutic Antibodies [Antibody samples were collected at weeks 1, 7, and 23 and every 6 months thereafter during treatment, and at the safety follow-up and follow-up visits. The mean follow-up time was 35.7 weeks.]

   Number of participants with human anti-panitumumab antibodies (HAPA) or anti-conatumumab antibodies measured by immunoassay.

7. Number of Participants With Adverse Events (AEs) [From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.]

   An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment, and includes any such occurrence (eg, sign, symptom, or diagnosis) or worsening of a pre-existing medical condition from the time that a participant has signed informed consent to the time of initiation of investigational product. The severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, according to the following: = Mild: Aware of sign or symptom, but easily tolerated = Moderate: Discomfort enough to cause interference with usual activity; = Severe: Incapacitating with inability to work or do usual activity; = Life-threatening: an event in which the patient was, in the view of the investigator, at risk of death at the time of the event; = Fatal.

8. Number of Participants With Post-baseline Laboratory Values Grade 3 or Higher [From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.]

   Laboratory values were assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (version 3.0) according to the following: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Life-threatening; 5 = Fatal.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum

• Radiographically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for Metastatic Colorectal Cancer. Progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment.

• At least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory

• Man or woman ≥ 18 years of age at the time of enrollment

• Hematologic function within the following limits:

• Absolute neutrophil count (ANC) > 1.0 x 10^9 cells/L

• Platelets ≥ 100 x 10^9/L

• Renal function within the following limits:

• Creatinine < 2.0 mg/dL

• Hepatic function within the following limits:

• Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases)

• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases)

• Bilirubin ≤ 2 x ULN

• Metabolic function within the following limits:

• Amylase ≤ 2 x ULN

• Lipase ≤ 2 x ULN

• Magnesium ≥ lower limit of normal

• Negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only)

• Must have received 1, 2, or 3 prior chemotherapy regimens for Metastatic Colorectal Cancer

• Competent to comprehend, sign, and date the independent ethics committee/institutional review board (IEC/IRB) approved written informed consent

Exclusion Criteria:

• History of other primary cancer, unless:

• Curatively resected non-melanomatous skin cancer

• Curatively treated cervical carcinoma in situ

• Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment

• Prior treatment with anti-epidermal growth factor receptor (EGFr) inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment

• Use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment

• Use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment

• Use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment

• Any investigational agent or therapy ≤ 30 days before enrollment

• Known allergy or hypersensitivity to any component of panitumumab and/or AMG 655

• History of or known presence of central nervous system (CNS) metastases

• History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan

• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment

• Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ Common Terminology Criteria for Adverse Events [CTCAE] grade 2 [CTCAE version 3.0])

• Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection

• Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion)

• Any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results

• Major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. Patients must have recovered from surgery related toxicities.

• Other investigational procedures are excluded

• Patient is currently pregnant or breast feeding

• Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence.

• Previously enrolled into this study

• Patient unwilling or unable to comply with study requirements

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Notice regarding posted summaries of trial results
• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00630786
• Other Study ID Numbers: 20060332; 2007-004722-25
• First Posted: Mar 7, 2008
• Last Update Posted: Feb 6, 2014
• Last Verified: Feb 1, 2014

• Additional relevant MeSH terms: Colorectal Neoplasms; Panitumumab; Conatumumab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 12 January 2008 through 6 November 2008

Arm/Group Title	Wild-type KRAS	Mutant KRAS	Unknown KRAS
Arm/Group Description	Participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with unknown Kirsten Rat Sarcoma Virus Oncogene (KRAS) type received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Period Title: Overall Study
STARTED	19	25	9
Received Study Medication	19	25	8
COMPLETED	18	23	7
NOT COMPLETED	1	2	2

Baseline Characteristics

Arm/Group Title	Wild-type KRAS	Mutant KRAS	Unknown KRAS	Total
Arm/Group Description	Participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with unknown Kirsten Rat Sarcoma Virus Oncogene (KRAS) type received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Total of all reporting groups
Overall Participants	19	25	8	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.53 (12.53)	64.32 (12.35)	58.63 (13.65)	62.42 (12.54)
Sex: Female, Male (Count of Participants)
Female	13 68.4%	11 44%	3 37.5%	27 51.9%
Male	6 31.6%	14 56%	5 62.5%	25 48.1%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	0 0%	1 4%	0 0%	1 1.9%
White or Caucasian	16 84.2%	24 96%	7 87.5%	47 90.4%
Black or African American	3 15.8%	0 0%	1 12.5%	4 7.7%

Outcome Measures

1. Primary Outcome

Title	Part 1: Number of Participants With Dose-limiting Toxicities
Description	A dose-limiting toxicity (DLT) was defined as any grade 3 or 4 conatumumab-related or combination (panitumumab and conatumumab)-related adverse event, or grade 3 or 4 laboratory abnormality that occurred during the first 4 weeks (28 days) of treatment with panitumumab and conatumumab. Anemia and lymphopenia were not considered DLTs. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to grade all adverse events and toxicities.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

DLT-evaluable patients were those who received ≥ 2 doses of panitumumab and conatumumab as scheduled (ie, weeks 1 and 3) and completed 4 weeks (28 days) of treatment, or had a DLT within the first 4 weeks (28 days) of treatment.

Arm/Group Title	Panitumumab Plus Conatumumab
Arm/Group Description	Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	5
Number [participants]	0 0%

2. Primary Outcome

Title	Number of Participants With an Objective Response
Description	An overall objective response of either a confirmed complete response or partial response, where the overall objective response was equivalent to the best overall response recorded for each participant from enrollment until disease progression or recurrence. Tumor response was assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Responses were confirmed no less than 4 weeks after the criteria for response were first met. Complete response defined as the disappearance of all target and non-target lesions and no new lesions. Partial response defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions.
Time Frame	Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).

Outcome Measure Data

Analysis Population Description

Subset of the Safety Analysis Set, composed of all enrolled participants who received at least one dose of study drug who had known Kirsten Rat Sarcoma Virus Oncogene (KRAS) status and Baseline measurable disease.

Arm/Group Title	Wild-type KRAS	Mutant KRAS
Arm/Group Description	Participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	18	25
Number [participants]	0 0%	0 0%

3. Secondary Outcome

Title	Progression-free Survival
Description	Kaplan-Meier estimate of the median time from enrollment to death from any cause or disease progression. Progressive disease is defined as at least a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the nadir SLD recorded since the treatment started, or the appearance of one or more new lesions, or the unequivocal progression of existing non-target lesions.
Time Frame	Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).

Outcome Measure Data

Analysis Population Description

Subset of the Safety Analysis Set, composed of all enrolled participants who received at least one dose of study drug who had known Kirsten Rat Sarcoma Virus Oncogene (KRAS) status.

Arm/Group Title	Wild-type KRAS	Mutant KRAS
Arm/Group Description	Participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	19	25
Median (95% Confidence Interval) [weeks]	10.0	7.1

4. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier estimate of time from enrollment to death from any cause
Time Frame	Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).

Outcome Measure Data

Analysis Population Description

Subset of the Safety Analysis Set, composed of all enrolled participants who received at least one dose of study drug, who had known Kirsten Rat Sarcoma Virus Oncogene (KRAS) status.

Arm/Group Title	Wild-type KRAS	Mutant KRAS
Arm/Group Description	Participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	19	25
Median (95% Confidence Interval) [months]	7.3	4.4

5. Secondary Outcome

Title	Number of Participants With Disease Control
Description	Disease control defined as participants with an overall objective response of complete response (CR), partial response (PR), or stable disease during the treatment period, assessed by the investigator according to the modified Response Evaluation Criteria in Solid Tumors (RECIST). Responses were confirmed no less than 4 weeks after the criteria for response were first met. CR defined as the disappearance of all target and non-target lesions and no new lesions. PR defined as either the disappearance of all target lesions with the persistence of one or more non-target lesion(s), or, at least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the Baseline SLD and the disappearance of all or the persistence of 1 or more non-target lesions. Stable disease defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the nadir LD since the treatment started.
Time Frame	Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).

Outcome Measure Data

Analysis Population Description

Subset of the Safety Analysis Set, composed of all enrolled participants who received at least one dose of study drug, who had known Kirsten Rat Sarcoma Virus Oncogene (KRAS) status.

Arm/Group Title	Wild-type KRAS	Mutant KRAS
Arm/Group Description	Participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	19	25
Number [participants]	8 42.1%	4 16%

6. Secondary Outcome

Title	Time to Response
Description	The interval in days from the first dose of study therapy to the date of first confirmed objective response. Calculated only for participants with an objective response.
Time Frame	Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).

Outcome Measure Data

Analysis Population Description

Patients with an overall objective response

Arm/Group Title	Wild-type KRAS	Mutant KRAS
Arm/Group Description	Participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	0	0

7. Secondary Outcome

Title	Duation of Response
Description	The interval in days from the first confirmed objective response to disease progression per the modified RECIST criteria or death. Calculated only for participants with an objective response.
Time Frame	Participants were evaluated for tumor response until radiographic disease progression or until the participant began another anticancer treatment (up to a maximum of 55.6 weeks).

Outcome Measure Data

Analysis Population Description

Patients with an overall objective response

Arm/Group Title	Wild-type KRAS	Mutant KRAS
Arm/Group Description	Participants with wild-type Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.	Participants with mutant Kirsten Rat Sarcoma Virus Oncogene (KRAS) received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	0	0

8. Secondary Outcome

Title	Number of Participants With Anti-therapeutic Antibodies
Description	Number of participants with human anti-panitumumab antibodies (HAPA) or anti-conatumumab antibodies measured by immunoassay.
Time Frame	Antibody samples were collected at weeks 1, 7, and 23 and every 6 months thereafter during treatment, and at the safety follow-up and follow-up visits. The mean follow-up time was 35.7 weeks.

Outcome Measure Data

Analysis Population Description

Safety analysis set, including all randomized patients who received at least 1 dose of investigational product. N indicates the number of patients with immunoassay results at the specified time points.

Arm/Group Title	Panitumumab Plus Conatumumab
Arm/Group Description	Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	52
Anti-panitumumab Antibody at Baseline (N=51)	0 0%
Anti-panitumumab Antibody Post-baseline (N=37)	2 10.5%
Anti-conatumumab Antibody at Baseline (N=50)	1 5.3%
Anti-conatumumab Antibody Post-baseline (N=37)	0 0%

9. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment, and includes any such occurrence (eg, sign, symptom, or diagnosis) or worsening of a pre-existing medical condition from the time that a participant has signed informed consent to the time of initiation of investigational product. The severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, according to the following: = Mild: Aware of sign or symptom, but easily tolerated = Moderate: Discomfort enough to cause interference with usual activity; = Severe: Incapacitating with inability to work or do usual activity; = Life-threatening: an event in which the patient was, in the view of the investigator, at risk of death at the time of the event; = Fatal.
Time Frame	From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, including all randomized patients who received at least one dose of investigational drug.

Arm/Group Title	Panitumumab Plus Conatumumab
Arm/Group Description	Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	52
Any adverse event	51 268.4%
Grade 3 adverse event	16 84.2%
Grade 4 adverse event	4 21.1%
Grade 5 adverse event	6 31.6%

10. Secondary Outcome

Title	Number of Participants With Post-baseline Laboratory Values Grade 3 or Higher
Description	Laboratory values were assessed using the National Cancer Institute (NCI) Common Toxicity Criteria (version 3.0) according to the following: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Life-threatening; 5 = Fatal.
Time Frame	From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, including all randomized patients who received at least one dose of investigational drug.

Arm/Group Title	Panitumumab Plus Conatumumab
Arm/Group Description	Participants received 10 mg/kg conatumumab and 6 mg/kg panitumumab administered on the same day by sequential intravenous (IV) infusions once every 2 weeks until progressive disease, intolerability, withdrawal, or death.
Measure Participants	52
Alanine Amino Transferase increase	4 21.1%
Alkaline Phosphatase increase	9 47.4%
Amylase increase	2 10.5%
Aspartate Amino Transferase increase	5 26.3%
Bicarbonate decrease	1 5.3%
Calcium increase	1 5.3%
Calcium decrease	3 15.8%
Glucose increase	1 5.3%
Lipase increase	2 10.5%
Magnesium decrease	4 21.1%
Magnesium increase	1 5.3%
Phosphorus decrease	1 5.3%
Sodium decrease	1 5.3%
Total Bilirubin increase	6 31.6%
Absolute Neutrophil Count decrease	7 36.8%
Hemoglobin decrease	4 21.1%
Lymphocytes decrease	7 36.8%

Adverse Events

Time Frame	From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Panitumumab + AMG 655
Arm/Group Description
All Cause Mortality
	Panitumumab + AMG 655
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Panitumumab + AMG 655
	Affected / at Risk (%)	# Events
Total	26/52 (50%)
Cardiac disorders
Atrial fibrillation	1/52 (1.9%)
Gastrointestinal disorders
Abdominal hernia obstructive	1/52 (1.9%)
Abdominal pain	3/52 (5.8%)
Diarrhoea	1/52 (1.9%)
Nausea	2/52 (3.8%)
Pneumoperitoneum	1/52 (1.9%)
Small intestinal obstruction	1/52 (1.9%)
Subileus	2/52 (3.8%)
Vomiting	3/52 (5.8%)
General disorders
Chills	2/52 (3.8%)
General physical health deterioration	4/52 (7.7%)
Performance status decreased	1/52 (1.9%)
Pyrexia	4/52 (7.7%)
Hepatobiliary disorders
Bile duct obstruction	1/52 (1.9%)
Biliary dilatation	1/52 (1.9%)
Hyperbilirubinaemia	1/52 (1.9%)
Jaundice	1/52 (1.9%)
Infections and infestations
Abdominal wall abscess	1/52 (1.9%)
Clostridial infection	1/52 (1.9%)
Folliculitis	1/52 (1.9%)
Gastroenteritis	1/52 (1.9%)
Peritonitis bacterial	1/52 (1.9%)
Pneumonia	1/52 (1.9%)
Rash pustular	1/52 (1.9%)
Sinusitis	1/52 (1.9%)
Metabolism and nutrition disorders
Dehydration	1/52 (1.9%)
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	1/52 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic	1/52 (1.9%)
Colorectal cancer	1/52 (1.9%)
Colorectal cancer metastatic	2/52 (3.8%)
Nervous system disorders
Cerebrovascular accident	1/52 (1.9%)
Sciatica	1/52 (1.9%)
Reproductive system and breast disorders
Pelvic fluid collection	1/52 (1.9%)
Respiratory, thoracic and mediastinal disorders
Respiratory distress	1/52 (1.9%)
Skin and subcutaneous tissue disorders
Erythema	1/52 (1.9%)
Other (Not Including Serious) Adverse Events
	Panitumumab + AMG 655
	Affected / at Risk (%)	# Events
Total	51/52 (98.1%)
Blood and lymphatic system disorders
Anaemia	3/52 (5.8%)
Eye disorders
Growth of eyelashes	7/52 (13.5%)
Gastrointestinal disorders
Abdominal distension	3/52 (5.8%)
Abdominal pain	9/52 (17.3%)
Abdominal pain upper	3/52 (5.8%)
Constipation	6/52 (11.5%)
Diarrhoea	9/52 (17.3%)
Nausea	16/52 (30.8%)
Oral pain	3/52 (5.8%)
Stomatitis	3/52 (5.8%)
Vomiting	17/52 (32.7%)
General disorders
Asthenia	7/52 (13.5%)
Chills	7/52 (13.5%)
Fatigue	20/52 (38.5%)
Mucosal inflammation	10/52 (19.2%)
Oedema peripheral	5/52 (9.6%)
Pain	5/52 (9.6%)
Pyrexia	9/52 (17.3%)
Infections and infestations
Folliculitis	5/52 (9.6%)
Paronychia	6/52 (11.5%)
Injury, poisoning and procedural complications
Procedural pain	3/52 (5.8%)
Investigations
Weight decreased	5/52 (9.6%)
Metabolism and nutrition disorders
Anorexia	14/52 (26.9%)
Hypomagnesaemia	10/52 (19.2%)
Musculoskeletal and connective tissue disorders
Muscle spasms	4/52 (7.7%)
Pain in extremity	7/52 (13.5%)
Nervous system disorders
Dysgeusia	3/52 (5.8%)
Neuralgia	3/52 (5.8%)
Respiratory, thoracic and mediastinal disorders
Cough	3/52 (5.8%)
Dyspnoea	7/52 (13.5%)
Skin and subcutaneous tissue disorders
Acne	6/52 (11.5%)
Dermatitis acneiform	3/52 (5.8%)
Dry skin	10/52 (19.2%)
Erythema	12/52 (23.1%)
Hair growth abnormal	3/52 (5.8%)
Pruritus	8/52 (15.4%)
Rash	28/52 (53.8%)
Scab	7/52 (13.5%)
Skin exfoliation	3/52 (5.8%)
Skin fissures	8/52 (15.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.