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Phase I/Ib Multiple Ascending Dose Study in China

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03523390
Recruitment Status : Completed
First Posted : May 14, 2018
Last Update Posted : May 13, 2021
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Brief Summary:
The purpose of this study is to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of Avelumab monotherapy in Chinese subjects.

Condition or disease Intervention/treatment Phase
Metastatic Solid Tumors Drug: Avelumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
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
Official Title: 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)
Actual Study Start Date : April 24, 2018
Actual Primary Completion Date : July 29, 2019
Actual Study Completion Date : February 8, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Avelumab 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

Primary Outcome Measures :
  1. Occurrence of Dose-limiting Toxicities (DLTs) [ Time Frame: Time from first treatment to planned assessment at Day 21 ]
  2. Area Under the Concentration-Time Curve From Time Zero to Time t (AUC0-t) of Avelumab [ Time Frame: Up to Month 15 ]
  3. Area Under the Concentration-Time Curve From Time Zero to tau (AUC0-tau) of Avelumab [ Time Frame: Up to Month 15 ]
  4. Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Avelumab [ Time Frame: Up to Month 15 ]
  5. Terminal Elimination Rate Constant (λz) of Avelumab [ Time Frame: Up to Month 15 ]
  6. Maximum Observed Serum Concentration (Cmax) of Avelumab [ Time Frame: Up to Month 15 ]
  7. Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab [ Time Frame: Up to Month 15 ]
  8. Last Quantifiable Concentration (Clast) of Avelumab [ Time Frame: Up to Month 15 ]
  9. Time to Reach Maximum Observed Serum Concentration (Tmax) for Avelumab [ Time Frame: Up to Month 15 ]
  10. Serum Decay Half-Life (t1/2) of Avelumab [ Time Frame: Up to Month 15 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Anti-Drug Antibodies (ADAs) Serum Titers [ Time Frame: Up to Day 115 ]
  3. Number of Subjects With Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) [ Time Frame: Up to Month 24 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03523390

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China, Guangzhou
Research site
Guangzhou, Guangzhou, China
China, Jilin
Research site
Changchun, Jilin, China
China, Zhejiang
Research site
Hangzhou, Zhejiang, China
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
Additional Information:
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Responsible Party: Merck KGaA, Darmstadt, Germany Identifier: NCT03523390    
Other Study ID Numbers: MS100070_0035
First Posted: May 14, 2018    Key Record Dates
Last Update Posted: May 13, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck KGaA, Darmstadt, Germany:
Metastatic Solid Tumors
Additional relevant MeSH terms:
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Antineoplastic Agents, Immunological
Antineoplastic Agents