A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03)
1 de dezembro de 2021 atualizado por: 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.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
395
Estágio
- Fase 1
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Arizona
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Scottsdale, Arizona, Estados Unidos, 85258
- Pinnacle Oncology Hematology
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06520
- Yale University School Of Medicine
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Florida
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Tampa, Florida, Estados Unidos, 33612-9497
- H. Lee Moffitt Cancer Center & Research Institute
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Maryland
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Baltimore, Maryland, Estados Unidos, 21231
- Johns Hopkins University
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Estados Unidos, 02215
- Dana Farber Cancer Institute
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Boston, Massachusetts, Estados Unidos, 02215
- Massachusetts General Hospital
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- University of Michigan Cancer Center
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New York
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Nassau
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North Carolina
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Huntersville, North Carolina, Estados Unidos, 28078
- Carolina Biooncology Institute
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Ohio
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Cincinnati, Ohio, Estados Unidos, 45219
- Christ Hospital
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37203
- Sarah Cannon Research Institute
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Nashville, Tennessee, Estados Unidos, 37232
- Vanderbilt-Ingram Cancer Ctr
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: 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
Outros nomes:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
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Experimental: 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
Outros nomes:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
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Experimental: 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
Outros nomes:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
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Experimental: 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
Outros nomes:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
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Experimental: CRC - 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
Outros nomes:
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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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
Prazo: 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
Prazo: 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
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Immunogenicity Assessment
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: 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 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)
Prazo: 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)
Prazo: 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 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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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Colaboradores
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Publicações Gerais
- 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.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
30 de outubro de 2008
Conclusão Primária (Real)
4 de fevereiro de 2013
Conclusão do estudo (Real)
22 de dezembro de 2020
Datas de inscrição no estudo
Enviado pela primeira vez
4 de agosto de 2008
Enviado pela primeira vez que atendeu aos critérios de CQ
7 de agosto de 2008
Primeira postagem (Estimativa)
8 de agosto de 2008
Atualizações de registro de estudo
Última Atualização Postada (Real)
3 de dezembro de 2021
Última atualização enviada que atendeu aos critérios de controle de qualidade
1 de dezembro de 2021
Última verificação
1 de novembro de 2021
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Neoplasias por Tipo Histológico
- Neoplasias
- Neoplasias Urológicas
- Neoplasias urogenitais
- Neoplasias por local
- Doenças renais
- Doenças Urológicas
- Adenocarcinoma
- Carcinoma
- Neoplasias Glandulares e Epiteliais
- Neoplasias Renais
- Carcinoma de Células Renais
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Antineoplásicos
- Agentes Antineoplásicos Imunológicos
- Inibidores de Ponto de Verificação Imunológica
- Nivolumabe
Outros números de identificação do estudo
- CA209-003
- MDX1106-03 (Outro identificador: BMS)
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Sim
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
produto fabricado e exportado dos EUA
Não
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .