Phase I/Ib Multiple Ascending Dose Study in China

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Metastatic Solid Tumors

Treatments: Drug: Avelumab 10 mg/kg Q2W; Drug: Avelumab 3 mg/kg Q2W; Drug: Avelumab 10 mg/kg QW; Drug: Avelumab 20 mg/kg Q2W

Study type: Interventional

Funder types: Industry

Identifiers

NCT03523390

MS100070_0035

Details and patient eligibility

About

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

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 4 patient groups

Avelumab 3 mg/kg Q2W

Experimental group

Treatment:

Drug: Avelumab 3 mg/kg Q2W

Avelumab 10 mg/kg Q2W

Experimental group

Treatment:

Drug: Avelumab 10 mg/kg Q2W

Avelumab 20 mg/kg Q2W

Experimental group

Treatment:

Drug: Avelumab 20 mg/kg Q2W

Avelumab 10 mg/kg QW

Experimental group

Treatment:

Drug: Avelumab 10 mg/kg QW