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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Administered by intravenous infusion
Administered by intravenous infusion
Part 1: Number of Participants With Dose-limiting Toxicities
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
Number of Participants With an Objective Response
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).
Progression-free Survival
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.
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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).
Overall Survival
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).
Number of Participants With Disease Control
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).
Time to Response
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).
Duation of Response
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).
Number of Participants With Anti-therapeutic Antibodies
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.
Number of Participants With Adverse Events (AEs)
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: 1. = Mild: Aware of sign or symptom, but easily tolerated 2. = Moderate: Discomfort enough to cause interference with usual activity; 3. = Severe: Incapacitating with inability to work or do usual activity; 4. = 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; 5. = Fatal.
Time frame: From first dose of investigational drug until 30 days after the last dose, up to a maximum of 50 weeks.
Number of Participants With Post-baseline Laboratory Values Grade 3 or Higher
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.