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Phase I/Ib Multiple Ascending Dose Study in China

Sponsor
Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Completed
CT.gov ID
NCT03523390
Collaborator
(none)
21
Enrollment
3
Locations
1
Arm
33.5
Actual Duration (Months)
7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
Phase 1

Study Design

Study Type:
Interventional
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.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 :
Apr 24, 2018
Actual Primary Completion Date :
Jul 29, 2019
Actual Study Completion Date :
Feb 8, 2021

Arms and Interventions

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 Names:
  • MSB0010718C

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Occurrence of Dose-limiting Toxicities (DLTs) [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 [Up to Month 15]

    3. Area Under the Concentration-Time Curve From Time Zero to tau (AUC0-tau) of Avelumab [Up to Month 15]

    4. Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Avelumab [Up to Month 15]

    5. Terminal Elimination Rate Constant (λz) of Avelumab [Up to Month 15]

    6. Maximum Observed Serum Concentration (Cmax) of Avelumab [Up to Month 15]

    7. Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab [Up to Month 15]

    8. Last Quantifiable Concentration (Clast) of Avelumab [Up to Month 15]

    9. Time to Reach Maximum Observed Serum Concentration (Tmax) for Avelumab [Up to Month 15]

    10. Serum Decay Half-Life (t1/2) of Avelumab [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 from first dose of study drug up to Day 175]

    2. Anti-Drug Antibodies (ADAs) Serum Titers [Up to Day 115]

    3. Number of Subjects With Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) [Up to Month 24]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research site Guangzhou Guangzhou China
    2 Research site Changchun Jilin China
    3 Research site Hangzhou Zhejiang China

    Sponsors and Collaborators

    • Merck KGaA, Darmstadt, Germany

    Investigators

    • Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck KGaA, Darmstadt, Germany
    ClinicalTrials.gov Identifier:
    NCT03523390
    Other Study ID Numbers:
    • MS100070_0035
    First Posted:
    May 14, 2018
    Last Update Posted:
    May 13, 2021
    Last Verified:
    May 1, 2021
    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
    Avelumab
    MSB0010718C
    Additional relevant MeSH terms:
    Avelumab

    Study Results

    No Results Posted as of May 13, 2021