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Phase I/Ib Multiple Ascending Dose Study in China

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ClinicalTrials.gov Identifier: NCT03523390
Recruitment Status : Completed
First Posted : May 14, 2018
Last Update Posted : May 13, 2021
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Tracking Information
First Submitted Date  ICMJE May 1, 2018
First Posted Date  ICMJE May 14, 2018
Last Update Posted Date May 13, 2021
Actual Study Start Date  ICMJE April 24, 2018
Actual Primary Completion Date July 29, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2018)
  • Occurrence of Dose-limiting Toxicities (DLTs) [ Time Frame: Time from first treatment to planned assessment at Day 21 ]
  • Area Under the Concentration-Time Curve From Time Zero to Time t (AUC0-t) of Avelumab [ Time Frame: Up to Month 15 ]
  • Area Under the Concentration-Time Curve From Time Zero to tau (AUC0-tau) of Avelumab [ Time Frame: Up to Month 15 ]
  • Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Avelumab [ Time Frame: Up to Month 15 ]
  • Terminal Elimination Rate Constant (λz) of Avelumab [ Time Frame: Up to Month 15 ]
  • Maximum Observed Serum Concentration (Cmax) of Avelumab [ Time Frame: Up to Month 15 ]
  • Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab [ Time Frame: Up to Month 15 ]
  • Last Quantifiable Concentration (Clast) of Avelumab [ Time Frame: Up to Month 15 ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) for Avelumab [ Time Frame: Up to Month 15 ]
  • Serum Decay Half-Life (t1/2) of Avelumab [ Time Frame: Up to Month 15 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2018)
  • Occurrence of Treatment-Emergent Adverse Events (AEs) and Treatment Related AEs According to National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 [ Time Frame: Time from first dose of study drug up to Day 175 ]
  • Anti-Drug Antibodies (ADAs) Serum Titers [ Time Frame: Up to Day 115 ]
  • Number of Subjects With Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) [ Time Frame: Up to Month 24 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/Ib Multiple Ascending Dose Study in China
Official Title  ICMJE A Phase I/Ib Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Avelumab in Chinese Subjects With Locally Advanced Unresectable or Metastatic Solid Tumors With Expansion to Selected Indication(s)
Brief Summary The purpose of this study is to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of Avelumab monotherapy in Chinese subjects.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
Subsequent cohorts of subjects treated at different dose levels in this study.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Solid Tumors
Intervention  ICMJE Drug: Avelumab
Subjects will receive an intravenous infusion of avelumab once every 2 weeks (q2w) or every week for the first 12 weeks and then q2w from Week 13 until progressive disease.
Other Name: MSB0010718C
Study Arms  ICMJE Experimental: Avelumab
Intervention: Drug: Avelumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 1, 2018)
21
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 8, 2021
Actual Primary Completion Date July 29, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed written informed consent prior to any study-related procedures are undertaken that are not part of standard patient management
  • Histologically or cytologically proven locally advanced unresectable or metastatic solid tumors, for which no standard therapy exists or standard therapy has failed
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
  • Availability of a recently obtained formalin-fixed, paraffin-embedded block containing tumor tissue (biopsy from a non-irradiated area within 6 months) or 12 or more unstained tumor slides suitable for biomarker detection
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as programmed death 1 (PD-1), PD-L1, cytotoxic T-lymphocyte antigen-4 (CTLA-4), 4-1BB, Lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) or anti-Cluster of Differentiation (CD)-127
  • Persisting toxicity related to prior therapy (Grade greater than equals to [>=] 2 National Cancer Institute- Common Terminology Criteria for Adverse Events [NCI-CTCAE] v4.03, except Grade less than [<] 3 neuropathy and alopecia of any grade)
  • Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of limited palliative bone-directed radiotherapy], immune therapy, or cytokine therapy except for erthyropoietin).
  • Concurrent immunosuppressive agents (except for corticosteroids at physiologic replacement dose, equivalent to less than equals to [<=] 10 milligram [mg] prednisone daily)
  • Severe hypersensitivity reactions to monoclonal antibodies (Grade >= 3 NCI-CTCAE v4.03)
  • Active brain metastases (except those treated locally, and have not been progressing for at least 2 weeks after the completion of therapy, with no steroid maintenance therapy required, and no ongoing neurological symptoms related to brain localization of the disease)
  • Any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
  • Other protocol defined exclusion criteria could apply
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT03523390
Other Study ID Numbers  ICMJE MS100070_0035
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck KGaA, Darmstadt, Germany
Study Sponsor  ICMJE Merck KGaA, Darmstadt, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
PRS Account Merck KGaA, Darmstadt, Germany
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP