A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies (MDX1106-01)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00441337
First received: February 27, 2007
Last updated: February 5, 2015
Last verified: February 2015
  Purpose

To evaluate the safety, tolerability, efficacy, and pharmacokinetics of MDX-1106 when administered to patients with advanced non-small cell lung cancer, colorectal cancer, malignant melanoma, clear cell renal cell cancer or hormone refractory prostate cancer


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Colorectal Cancer
Malignant Melanoma
Renal Cancer
Prostate Cancer
Biological: MDX-1106
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open Label, Dose-escalation, Safety and Pharmacokinetic Study of MDX-1106 in Patients With Selected or Relapsed Malignancies

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population [ Time Frame: Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation ] [ Designated as safety issue: Yes ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Severe=All Grade 3 or 4 events. Death=during the study and up to 28 days past study discontinuation. AEs graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. irAEs=unknown etiology, associated with study drug and consistent with an immune phenomenon. DLT: ≥Gr 3 AE(s) or lab abnormality without alternative explanation other than drug.

  • Geometric Mean Maximum Serum Concentration (Cmax) Observed Post-Single Dose [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated enzyme-linked immunosorbent assay (ELISA) method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The pharmacokinetic (PK) parameter of Cmax was measured in micrograms per milliliter (µg/mL).

  • Median Time at Which the Maximum Serum Concentration Occurred (Tmax) Post-Single Dose [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of Tmax was measured in hours (h).

  • Geometric Mean Area Under the Curve (AUC) From Time of Dosing to Time of Last Observation (0-T) and Extrapolated to Infinity (INF) Observed Post-Single Dose [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    AUC(0-T): Area under the concentration-time curve from the time of dosing to the time of the last observation. AUC(INF): Area under the curve from the time of dosing extrapolated to infinity. Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameters of AUC(0-T) and AUC (INF) were measured in micrograms*hours per milliliter (µg*h/mL).

  • Mean Elimination Half-life (T-HALF) Post-Single Dose [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of T-HALF was measured in days.

  • Geometric Mean Total Body Clearance of Drug From Serum (CLT) Post-Single Dose [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of CLT was measured in milliliters per hour per kilogram body weight (mL/h/kg).

  • Mean Volume of Distribution (Vz) Post-Single Dose [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    Nivolumab in human serum was assayed during the period of known analyte stability and reported as final data for this study by PPD® (Richmond, Virginia) using a cross-validated ELISA method. For the single dose (Day 1), serum concentrations of nivolumab were assessed: prior to dosing, at 30 minutes (during dosing), immediately post-dose, and 30 minutes post-infusion end time; at 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion end time; and on Days 8, 15, 22, 29, 43, 57, 71, and 85. The PK parameter of Vz was measured in milliliters per kilogram of body weight (mL/kg).

  • Percent of Participants With Best Overall Response Rate in Safety Population and in Tumor Evaluable Population [ Time Frame: Day 1 up to 2 Years. ] [ Designated as safety issue: No ]
    The Best Overall Response Rate (BORR) was defined as the number of participants who had a confirmed complete response (CR) or partial response (PR) during the study divided by the total number of participants evaluated. Response was based on tumor assessment for both target and non-target lesions using: Clinical examination; Chest X-ray; Computed Tomography and Magnetic Resonance Imaging; Bone scan; Ultrasound. Per National Cancer Institute Response Evaluation Criteria in Solid Tumors (RECIST) v1.0, best overall response (BOR) for tumors was confirmed CR or PR. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter. Confidence intervals (CIs) were computed using the Clopper and Pearson method.

  • Percent of Participants With Prostate-Specific Antigen (PSA) Response After the First Dose by Day 85 In Participants With Hormone-Refractory Prostate Adenocarcinoma (HRPC) [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    The PSA response rate was defined as the number of participants who had at least a 50% decrease of the PSA value from the PSA reference value divided by the total number of participants evaluated (percent of participants). PSA reference value was the PSA concentration measured immediately prior to dosing on Day 1. PSA response was assessed using the Recommendations from the National Cancer Institute Prostate-Specific Antigen Working Group. A PSA response had to be confirmed at least 4 weeks after first response. 95% exact CIs were computed using the Clopper and Pearson method.


Secondary Outcome Measures:
  • Number of Participants With Best Overall Response (BOR) by Category in Safety Population [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    Measurable and non-measurable disease/target lesions were evaluated according to National Cancer Institute standardized RECIST.Complete Response (CR)=disappearance of all target and non-target lesions and no new lesions; Partial Response=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter; Stable disease (SD)=neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since treatment; PD=at least a 20% increase in the sum of the longest diameter recorded since screening, or the appearance of one or more new lesions. BOR was recorded between the first tumor assessment and last tumor assessment. CR and PR had to be confirmed by repeat assessment no less than 4 weeks after the criteria were first met. SD assessment must have met the criteria at least once at or after Week 12.

  • Percentage of Participants With Disease Control and Major Durable Disease Control [ Time Frame: Day 1 to 2 Years ] [ Designated as safety issue: No ]
    Disease control rate was defined as number of participants whose Best Overall Response (BOR) was complete response (CR), partial response (PR), or stable disease (SD) divided by the total number of participants. Major durable disease control rate was defined as the total number of participants whose BOR was CR, PR, or SD ≥24 weeks, divided by the total number of participants. Per RECIST v 1.0, BOR for tumors was confirmed CR or PR. CR=disappearance of all target and non-target lesions; PR=at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter since treatment; SD=neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD. PD=at least a 20% increase in the sum of the longest diameter recorded since screening, or the appearance of one or more new lesions. 95% CIs were computed using the Clopper and Pearson method.

  • Median Time to Tumor Response and Duration of Tumor Response [ Time Frame: Day 1 to 2 Years ] [ Designated as safety issue: No ]
    Time to tumor response: from the date of first dose to the first date of tumor response (CR or PR confirmed at least 4 weeks later); for nonresponders, it was censored at the date of the maximum tumor assessment time in the dose cohort by the end of study. Duration of tumor response was calculated from the first date of response of CR or PR to the date of the first PD or the date of death if a participant died due to disease progression (whichever occurred first). Duration of response was censored at the last tumor assessment date by the end of study if a responder did not have PD or death. Nonresponders had the duration of response as an event of 0 days.

  • Time to Tumor Progression and Tumor Progression Free Survival [ Time Frame: Day 1 to 2 Years ] [ Designated as safety issue: No ]
    Time to tumor progression (TTP) was measured in days from date of the first dose to the date of the first PD or the date of death if due to PD. For those who died without PD it was censored at the date of death. TTP was censored at the last tumor assessment by the end of study if a participant did not have PD or death. Tumor progression free survival (PFS) was measured in days from the date of first dose to the date of the first disease progression or to the date of death. PFS was censored at the last tumor assessment date by the end of study if a participant did not have PD or death.

  • Median Time to PSA Progression in Days and Median PSA Progression Free Survival in Days in PSA Evaluable Population [ Time Frame: Day 1 to 2 Years ] [ Designated as safety issue: No ]
    Time to PSA progression: first dose to first PSA progression. Missing date of progression was censored: if death during the study, time to progression was right-censored at last PSA assessment; if no progression from first dose and still alive at end of study, time to progression was right-censored at last PSA assessment by end of study; if no PSA progression and one has discontinued from the study (other than death or PSA progression), time to progression was right-censored at last PSA assessment. PSA progression free survival (PFS): first dose to first PSA progression or death, whichever comes first. Missing date of progression was censored: if one did not have PSA progression from first dose and was still alive at end of study, PSA PFS was right-censored at last PSA assessment; if one does not have any progression and discontinued from the study for reasons other than death or progression, PFS was right-censored at last assessment. CI computed using Brookmeyer and Crowley method.

  • Mean Change From Baseline in PSA Relative Velocity at Days 29, 57, and 85 With Cycle 1 in PSA Evaluable Population [ Time Frame: Day 29, Day 57, Day 85 ] [ Designated as safety issue: No ]
    PSA relative velocity (PSA RV) was defined as = (d[PSA]/dt)/ [PSA], where [PSA] =concentration of PSA, and t= time, and in the limit reflects the instantaneous change in PSA levels as a fraction of total PSA level. Decreases in PSA RV may occur while measured [PSA] is still rising, and may indicate that continued therapy may lead to a treatment benefit, particularly in the setting of immunotherapy, where expansion of an effective immune response is likely to require weeks to mature. Baseline PSA RV was based on the velocity of last PSA measurement before the first infusion of study drug and the screening PSA measurement.

  • Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population [ Time Frame: Baseline, Day 2, Day 85, Day 113 ] [ Designated as safety issue: Yes ]
    12-lead ECGs were performed at screening, baseline, Day 2 and at completion of the dose cycle (Day 85 in first dose cycle). In those participants undergoing re-treatment, ECG was repeated at the completion of the re-treatment. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. PR, QRS and QT interval were measured in milliseconds (msec).

  • Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population [ Time Frame: Baseline, Day 1 ] [ Designated as safety issue: Yes ]
    Diastolic blood pressures (DBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Post infusion DBPs are presented in the 0.3 mg cohort at: 21, 36, 51, 66, 82, 97, 112, 127, 157 minutes post infusion, and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean DBP on Day 1 for first dose (cycle 1) are presented below.

  • Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population [ Time Frame: Baseline, Day 1 ] [ Designated as safety issue: Yes ]
    Systolic blood pressures (SBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion SBPs are presented in the 0.3 mg cohort at: 21, 36, 51, 66, 82, 97, 112, 127, 157 minutes post infusion, and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean SBP on Day 1 for first dose (cycle 1) are presented below.

  • Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population [ Time Frame: Baseline, Day 1 ] [ Designated as safety issue: Yes ]
    Diastolic blood pressures (DBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion DBPs are presented in the 1 mg, 3 mg and 10 mg cohorts at: 15, 30, 45, 60, 75, and 90 minutes post infusion and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean DBP on Day 1 for first dose (cycle 1) are presented below.

  • Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population [ Time Frame: Baseline, Day 1 ] [ Designated as safety issue: Yes ]
    Systolic blood pressures (SBPs) measured in millimeters of mercury (mmHg) were obtained while the participant was seated. Baseline, Infusion (0 minutes) and Post infusion SBPs are presented in the 1 mg, 3 mg and 10 mg cohorts at: 15, 30, 45, 60, 75, and 90 minutes post infusion and at 1, 2, 3, 4, 6, 8 hours post infusion. Baseline was defined as the last measurement before the first dose of study drug, which was calculated from pre-dose or from screening if pre-dose was not available. Mean SBPs on Day 1 for first dose (cycle 1) are presented below.


Enrollment: 39
Study Start Date: August 2006
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 0.3 mg/kg MDX-1106 drug
0.3 milligrams (mg) MDX-1106 drug (nivolumab) per kilogram (kg) of body weight (mg/kg) was administered in a single intravenous (IV) infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks).
Biological: MDX-1106
patients will receive a single dose of MDX-1106 as a 60 minute infusion.
Other Names:
  • MDX-1106
  • nivolumab
Experimental: 1 mg/kg MDX-1106 drug
1 mg MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks).
Biological: MDX-1106
patients will receive a single dose of MDX-1106 as a 60 minute infusion.
Other Names:
  • MDX-1106
  • nivolumab
Experimental: 3 mg/kg MDX-1106 drug
3 mgs MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks).
Biological: MDX-1106
patients will receive a single dose of MDX-1106 as a 60 minute infusion.
Other Names:
  • MDX-1106
  • nivolumab
Experimental: 10 mg/kg MDX-1106 drug
10 mgs MDX-1106 drug (nivolumab) per kg of body weight (mg/kg) was administered in a single IV infusion. If criteria were met, 2 additional doses could be administered (1 every 4 weeks).
Biological: MDX-1106
patients will receive a single dose of MDX-1106 as a 60 minute infusion.
Other Names:
  • MDX-1106
  • nivolumab

Detailed Description:

Six patients enrolled at each dose level of 0.3, 1.0, 3.0 and 10mg/kg; the remaining 10 to 15 patients may subsequently be enrolled at a dose at or below the maximum tolerated dose (MTD) during the dose-escalation portion of the study. Patients who respond may receive additional doses of drug.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed/refractory non-small cell lung cancer, colorectal adenocarcinoma, malignant melanoma, renal (clear) cell carcinoma, or hormone-refractory prostate adenocarcinoma
  • Prior treatment must have been completed at least 4 weeks prior to enrollment
  • No untreated primary or metastatic brain or meningeal tumors
  • ECOG PS 0 or 1
  • Meet all screening laboratory values

Exclusion Criteria:

  • History of severe hypersensitivity reactions to other monoclonal antibodies
  • Active autoimmune disease or a documented history of autoimmune disease
  • Prior therapy with an anti-PD-1 or anti-CTLA-4 antibody
  • Active infection
  • Concurrent medical condition requiring the use of immunosuppressive medications
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00441337

Locations
United States, Maryland
Johns Hopkins Unv., School of Medicine
Baltimore, Maryland, United States, 21231
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University School of Medicine - Barnes Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, North Carolina
Carolina BioOncology Institute, PLLC
Huntersville, North Carolina, United States, 28078
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00441337     History of Changes
Other Study ID Numbers: CA209-001 ST, MDX1106-01
Study First Received: February 27, 2007
Results First Received: January 21, 2015
Last Updated: February 5, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
malignancies
cancer
non small cell lung cancer
lung cancer
colorectal cancer
adenocarcinoma
melanoma
malignant melanoma
renal cancer
renal carcinoma
carcinoma
prostate cancer
prostate adenocarcinoma
Recurrent or treatment refractory malignancies

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Colorectal Neoplasms
Kidney Neoplasms
Melanoma
Prostatic Neoplasms
Adenocarcinoma
Bronchial Neoplasms
Carcinoma
Carcinoma, Bronchogenic
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Intestinal Diseases
Intestinal Neoplasms
Kidney Diseases
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors

ClinicalTrials.gov processed this record on July 01, 2015