A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03)
1 décembre 2021 mis à jour par: Bristol-Myers Squibb
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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
395
Phase
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Arizona
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Scottsdale, Arizona, États-Unis, 85258
- Pinnacle Oncology Hematology
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Connecticut
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New Haven, Connecticut, États-Unis, 06520
- Yale University School Of Medicine
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Florida
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Tampa, Florida, États-Unis, 33612-9497
- H. Lee Moffitt Cancer Center & Research Institute
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Maryland
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Baltimore, Maryland, États-Unis, 21231
- Johns Hopkins University
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Massachusetts
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Boston, Massachusetts, États-Unis, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, États-Unis, 02215
- Dana Farber Cancer Institute
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Boston, Massachusetts, États-Unis, 02215
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, États-Unis, 48109
- University of Michigan Cancer Center
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New York
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New York, New York, États-Unis, 10065
- Memorial Sloan Kettering Nassau
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North Carolina
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Huntersville, North Carolina, États-Unis, 28078
- Carolina Biooncology Institute
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Ohio
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Cincinnati, Ohio, États-Unis, 45219
- Christ Hospital
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Tennessee
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Nashville, Tennessee, États-Unis, 37203
- Sarah Cannon Research Institute
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Nashville, Tennessee, États-Unis, 37232
- Vanderbilt-Ingram Cancer Ctr
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Melanoma - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
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Expérimental: RCC - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
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Expérimental: mCRPC - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
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Expérimental: NSCLC - BMS-936558 (MDX-1106)
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Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
|
|
Expérimental: CRC - BMS-936558 (MDX-1106)
|
Solution, Intravenous, 0.1 mg/kg - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs
Délai: Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years
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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. |
Day 1 to 70 days following last dose of study drug up to June 2013, approximately 4 years
|
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Number of Participants With Abnormal Serum Chemistry Laboratory Values
Délai: Day 1 up to June 2013, approximately 4 years
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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.
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Day 1 up to June 2013, approximately 4 years
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Number of Participants With Abnormal Hematology Laboratory Values
Délai: Day 1 up to June 2013, approximately 4 years
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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.
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Day 1 up to June 2013, approximately 4 years
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Immunogenicity Assessment
Délai: Day 1 up to June 2013, approximately 4 years
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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.
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Day 1 up to June 2013, approximately 4 years
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Objective Response Rate
Délai: Day 1 up to June 2013, approximately 4 years
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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.
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Day 1 up to June 2013, approximately 4 years
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Duration of Tumor Response
Délai: Day 1 up to June 2013, approximately 4 years
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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.
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Day 1 up to June 2013, approximately 4 years
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Geometric Mean Maximum Serum Concentration (Cmax)
Délai: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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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).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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Median Time of Maximum Serum Concentration (Tmax)
Délai: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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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).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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Geometric Mean Area Under the Curve (AUC[TAU]) in One Dosing Interval Observed Post-Single Dose
Délai: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
|
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).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycles 1 and 3
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Geometric Mean Total Body Clearance of Drug From Serum (CLT)
Délai: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
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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).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
|
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Mean Effective Half-life (T-HALFeff)
Délai: 1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
|
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).
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1,4,8,24,48 and 96 hours post-dose timepoints on Day 1 of cycle 3
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- 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.
- 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.
- 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.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
30 octobre 2008
Achèvement primaire (Réel)
4 février 2013
Achèvement de l'étude (Réel)
22 décembre 2020
Dates d'inscription aux études
Première soumission
4 août 2008
Première soumission répondant aux critères de contrôle qualité
7 août 2008
Première publication (Estimation)
8 août 2008
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
3 décembre 2021
Dernière mise à jour soumise répondant aux critères de contrôle qualité
1 décembre 2021
Dernière vérification
1 novembre 2021
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Tumeurs par type histologique
- Tumeurs
- Tumeurs urologiques
- Tumeurs urogénitales
- Tumeurs par site
- Maladies rénales
- Maladies urologiques
- Adénocarcinome
- Carcinome
- Tumeurs, glandulaires et épithéliales
- Tumeurs rénales
- Carcinome à cellules rénales
- Mécanismes moléculaires de l'action pharmacologique
- Agents antinéoplasiques
- Agents antinéoplasiques immunologiques
- Inhibiteurs de point de contrôle immunitaire
- Nivolumab
Autres numéros d'identification d'étude
- CA209-003
- MDX1106-03 (Autre identifiant: BMS)
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
Étudie un produit d'appareil réglementé par la FDA américaine
Non
produit fabriqué et exporté des États-Unis.
Non
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .