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Metastatic Castration-resistant Prostrate CancerPhase 1MDX1106-03NCT00730639

A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies

A Phase 1 study testing BMS-936558 (MDX-1106) in people with Metastatic Castration-resistant Prostrate Cancer and Renal Cell Carcinoma, run by Bristol-Myers Squibb at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the safety and effectiveness of MDX-1106 in patients with certain types of cancer. Another purpose is to determine how MDX-1106 is absorbed and distributed within the body, and how it's eventually eliminated. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BMS-936558 (MDX-1106)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
395 participants
Where
13 sitesUnited States
Study dates
30 Oct 2008to 22 Dec 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must have mCRPC,RCC, MEL, Non-small-cell lung cancer (NSCLC), or Colorectal Cancer (CRC), that is advanced (non-resectable), or recurrent and for which no alternative, curative standard exists
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Must have at least 1 measurable lesion
  • Subjects with mCRPC and with only non-measurable bone lesions must have either progression new lesions or have Prostate-specific antigen (PSA) progression within the 6-week period before study administration
  • At least 1 and up to 5 prior systemic therapies for advanced/recurrent disease
  • Prior treated brain or meningeal metastases must be without Magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids for at least 2 weeks before study drug administration
Show all 9Show fewer
  • Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks prior to study drug administration
  • Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids must be discontinued at least 2 weeks before study drug administration
  • Prior surgery that required general anesthesia must be completed at least 2 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration

Who cannot join

  • History of severe hypersensitivity reactions to other Monoclonal antibody (mAb)s
  • Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy
  • Prior therapy with an anti-Programmed death-1 (PD-1), anti-PD-L1, anti-PD-L2, or anti- Cytotoxic t-lymphocyte antigen-4 (CTLA-4) antibody (or any other antibody targeting T cell co-stimulation pathways)
  • Known history of Human Immunodeficiency Virus
  • Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
  • Underlying medical conditions that will make the administration of study drug hazardous
  • Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids
  • Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • University Of Michigan Cancer Center

    Ann Arbor, Michigan, 48109

  • Johns Hopkins University

    Baltimore, Maryland, 21231

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Massachusetts General Hospital

    Boston, Massachusetts, 02215

  • Christ Hospital

    Cincinnati, Ohio, 45219

  • Carolina Biooncology Institute

    Huntersville, North Carolina, 28078

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Vanderbilt-Ingram Cancer Ctr

    Nashville, Tennessee, 37232

  • Yale University School Of Medicine

    New Haven, Connecticut, 06520

  • Memorial Sloan Kettering Nassau

    New York, New York, 10065

  • Pinnacle Oncology Hematology

    Scottsdale, Arizona, 85258

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612-9497

Other trials in United States

About this study

Official title: A Phase 1, Open-Label, Multicenter, Multidose, Dose Escalation Study of BMS-936558 (Nivolumab) in Subjects With Selected Advanced or Recurrent Malignancies

The purpose of this study is to determine the safety and effectiveness of MDX-1106 in patients with certain types of cancer. Another purpose is to determine how MDX-1106 is absorbed and distributed within the body, and how it's eventually eliminated.

Being tested
BMS-936558 (MDX-1106)
Medical subject headings
Carcinoma, Renal Cell, Melanoma, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BMS-936558 (MDX-1106)Biological

    Also called BMS-936558

    Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response

  • BMS-936558 (MDX-1106)Biological

    Also called BMS-936558

    Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response

  • BMS-936558 (MDX-1106)Biological

    Also called BMS-936558

    Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response

  • BMS-936558 (MDX-1106)Biological

    Also called BMS-936558

    Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response

  • BMS-936558 (MDX-1106)Biological

    Also called BMS-936558

    Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response

Study groups in NCT00730639
Study groupRoleWhat they receive
Melanoma - BMS-936558 (MDX-1106)ExperimentalNot described
Receives: Biological: BMS-936558 (MDX-1106)
RCC - BMS-936558 (MDX-1106)ExperimentalNot described
Receives: Biological: BMS-936558 (MDX-1106)
mCRPC - BMS-936558 (MDX-1106)ExperimentalNot described
Receives: Biological: BMS-936558 (MDX-1106)
NSCLC - BMS-936558 (MDX-1106)ExperimentalNot described
Receives: Biological: BMS-936558 (MDX-1106)
CRC - BMS-936558 (MDX-1106)ExperimentalNot described
Receives: Biological: BMS-936558 (MDX-1106)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs

    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. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v15.1) and graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.

    Measured: Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years

  2. Number of Participants With Abnormal Serum Chemistry Laboratory Values

    Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine and Total Bilirubin. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Abnormal values for ALP, ALT and AST were based on grades; Gr 1: > 1.0 - 2.5 * upper limits of normal (ULN); Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Abnormal values for Creatinine were based on Gr 1: > 1.0 - 1.5*ULN; Gr 2: > 1.5 - 3.0*ULN; Gr 3: > 3.0 - 6.0*ULN; Gr 4: > 6.0*ULN. Abnormal values for Total Bilirubin were based on Gr 1: > 1.0 - 1.5 * upper limits of normal (ULN); Gr 2: > 1.5 - 3.0 * ULN; Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN.

    Measured: Day 1 up to June 2013, approximately 4 years

  3. Number of Participants With Abnormal Hematology Laboratory Values

    Hemoglobin, Lymphocytes, Neutrophils, Platelets and Leukocytes. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Abnormal values for Hemoglobin were based on Gr 1: 10.0 - less than (<) lower limit of normal (LLN); Gr 2: 8.0 - < 10.0; Gr 3: 6.5 - < 8.0; Gr 4: < 6.5. Abnormal values for Lymphocytes were based on Gr 1: 0.8 - < 1.5; Gr 2: 0.5 - < 0.8; Gr 3): 0.2 - < 0.5; Gr 4: < 0.2. Abnormal values for Neutrophils were based on Gr 1: 1.5 - < 2.0; Gr 2: 1.0 - < 1.5; Gr 3: 0.5 - < 1.0; Gr 4: < 0.5. Abnormal values for Platelets were based on Gr 1: 75.0 - < lower limits of normal (LLN); Gr 2: 50.0 - < 75.0; Gr 3: 25.0 - < 50.0; Gr 4: < 25.0. Abnormal values for Leukocytes were based on Gr 1: 3.0 - < LLN; Gr 2: 2.0 - < 3.0; Gr 3: 1.0 - < 2.0; Gr4: < 1.0.

    Measured: Day 1 up to June 2013, approximately 4 years

Secondary outcomes (8)

  1. Immunogenicity Assessment

    Classification of participants host immune response was based on the following definitions: Anti-Drug Antibody (ADA) Positive Subjects have with at least one ADA positive sample at any time after initiation of treatment. ADA positive subjects were further classified into categories with Persistent Positive defined as an ADA positive sample at 2 or more sequential timepoints at least 8 weeks apart.

    Measured: Day 1 up to June 2013, approximately 4 years

  2. Objective Response Rate

    Tumor response was evaluated by the sponsor based on tumor assessments by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Objective response rate (ORR) was defined as the proportion of participants who's confirmed best overall response (BOR) is either complete (CR) or partial (PR), where the denominator is the number of treated participants in the population of interest. Response was based on tumor measurements. Responders= complete response (CR) or partial response (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. 95% Confidence intervals (CIs) were computed using the Clopper Pearson method.

    Measured: Day 1 up to June 2013, approximately 4 years

  3. Duration of Tumor Response

    Duration of tumor response (DOR) was calculated from the first date of response of complete response (CR) or partial response (PR) to the date of the first progressive disease (PD) or the date of death. Duration of response was censored at the last tumor assessment date if a responder did not have PD or death. Nonresponders were not included in the analysis. Median DOR was estimated by Kaplan-Meier analysis.

    Measured: Day 1 up to June 2013, approximately 4 years

  4. Geometric Mean Maximum Serum Concentration (Cmax)

    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated enzyme-linked immunosorbent assay (ELISA). Blood samples were assessed at all doses from a subset of participants. The pharmacokinetic (PK) parameter of Cmax was measured in micrograms per milliliter (µg/mL).

    Measured: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3

  5. Median Time of Maximum Serum Concentration (Tmax)

    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed Blood samples were assessed at all doses from a subset of participants. The PK parameter of Tmax was measured in hours (h).

    Measured: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3

  6. Geometric Mean Area Under the Curve (AUC[TAU]) in One Dosing Interval Observed Post-Single Dose

    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed at all doses from a subset of participants. The PK parameter of AUC was measured in micrograms*hours per milliliter (μg*h/mL).

    Measured: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3

  7. Geometric Mean Total Body Clearance of Drug From Serum (CLT)

    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples Blood samples were assessed at all doses from a subset of participants. The PK parameter of CLT was measured in milliliters per hour (mL/h).

    Measured: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3

  8. Mean Effective Half-life (T-HALFeff)

    Nivolumab in human serum was assayed by PPD® (Richmond, Virginia) using a cross-validated ELISA. Blood samples were assessed at all doses from a subset of participants. The PK parameter of T-HALFeff was measured in hours (h).

    Measured: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2008 (estimated)
  2. Study start30 Oct 2008
  3. Primary completion4 Feb 2013
  4. Study completion22 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
395 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00730639
Sponsor's protocol ID
CA209-003
Other IDs
MDX1106-03
Acronym
MDX1106-03
Status last verified
Nov 2021
First submitted
4 Aug 2008
Last updated
3 Dec 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Long GV, Larkin J, Schadendorf D, Grob JJ, Lao CD, Marquez-Rodas I, Wagstaff J, Lebbe C, Pigozzo J, Robert C, Ascierto PA, Atkinson V, Postow MA, Atkins MB, Sznol M, Callahan MK, Topalian SL, Sosman JA, Kotapati S, Thakkar PK, Ritchings C, Pe Benito M, Re S, Soleymani S, Hodi FS. Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma. J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.

    PubMed 39504507

  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Drilon A, Wolchok JD, Carvajal RD, McHenry MB, Hosein F, Harbison CT, Grosso JF, Sznol M. Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non-Small Cell Lung Cancer Treated With Nivolumab. JAMA Oncol. 2019 Oct 1;5(10):1411-1420. doi: 10.1001/jamaoncol.2019.2187.

    PubMed 31343665

  • Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3.

    PubMed 24590637

  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

    PubMed 22658127

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BMS-936558 (MDX-1106) in people with Metastatic Castration-resistant Prostrate Cancer and Renal Cell Carcinoma, run by Bristol-Myers Squibb at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs (time frame: Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00730639, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2021.

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