A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03)
2021年12月1日 更新者：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.
調査の概要
状態
完了
研究の種類
介入
入学 (実際)
395
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Arizona
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Scottsdale、Arizona、アメリカ、85258
- Pinnacle Oncology Hematology
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Connecticut
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New Haven、Connecticut、アメリカ、06520
- Yale University School Of Medicine
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Florida
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Tampa、Florida、アメリカ、33612-9497
- H. Lee Moffitt Cancer Center & Research Institute
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Maryland
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Baltimore、Maryland、アメリカ、21231
- Johns Hopkins University
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Massachusetts
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Boston、Massachusetts、アメリカ、02215
- Beth Israel Deaconess Medical Center
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Boston、Massachusetts、アメリカ、02215
- Dana Farber Cancer Institute
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Boston、Massachusetts、アメリカ、02215
- Massachusetts General Hospital
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- University of Michigan Cancer Center
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New York
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New York、New York、アメリカ、10065
- Memorial Sloan Kettering Nassau
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North Carolina
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Huntersville、North Carolina、アメリカ、28078
- Carolina Biooncology Institute
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Ohio
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Cincinnati、Ohio、アメリカ、45219
- Christ Hospital
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Tennessee
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Nashville、Tennessee、アメリカ、37203
- Sarah Cannon Research Institute
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt-Ingram Cancer Ctr
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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
他の名前：
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
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実験的：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
他の名前：
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
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実験的：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
他の名前：
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
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実験的：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
他の名前：
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
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実験的：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
他の名前：
Solution, Intravenous, 1 - 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
Solution, Intravenous, 10 mg/kg, Every 2 weeks, 3 years depending on response
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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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
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Immunogenicity Assessment
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2008年10月30日
一次修了 (実際)
2013年2月4日
研究の完了 (実際)
2020年12月22日
試験登録日
最初に提出
2008年8月4日
QC基準を満たした最初の提出物
2008年8月7日
最初の投稿 (見積もり)
2008年8月8日
学習記録の更新
投稿された最後の更新 (実際)
2021年12月3日
QC基準を満たした最後の更新が送信されました
2021年12月1日
最終確認日
2021年11月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。