Clinical trial NCT03523390: Phase I/Ib Multiple Ascending Dose Study in China
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Solid Tumors
Keywords: Metastatic Solid Tumors
Avelumab
MSB0010718C
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-05-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Subsequent cohorts of subjects treated at different dose levels in this study.
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With of Dose-limiting Toxicities (DLTs) According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03
timeFrame: Day 1 to Day 21
measure: Area Under the Serum Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Area Under the Serum Concentration-Time Curve During a Dosing Interval (AUCtau) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Terminal Elimination Rate Constant (Lambda z) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Maximum Observed Serum Concentration (Cmax) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Last Quantifiable Serum Concentration (Clast) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Serum Trough Concentration Levels (Ctrough) of Avelumab
timeFrame: Day 1: within 2 hours prior to 1 hour infusion
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Apparent Terminal Half Life (t1/2) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Dose Normalized Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Dose Normalized Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau/Dose) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
measure: Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Avelumab
timeFrame: Day 1: within 2 hours prior to and at the end of the 1-hour infusion, and at 0.5, 1, 2, 4, 6, and 12 hours after the end of the infusion
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs According to National Cancer Institute- Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
timeFrame: Time from first study treatment up to 139 weeks
measure: Number of Participants With at Least 1 Positive Anti-Avelumab Antibodies (ADA)
timeFrame: Time from first study treatment up to 139 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Research site
state: Guangzhou
city: Changchun
country: China
facility: Research site
state: Jilin
city: Hangzhou
country: China
facility: Research site
state: Zhejiang
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Wu YL, Cheng Y, Chen H, Tu H, Xu C, Wang Z, Liu Y, Xin Y, Lou H, Wang W, Chin K, Li D, Zhao D, Gao Y, Xu W, Pan H. Phase I/Ib dose-escalation study of avelumab in Chinese patients with advanced solid tumors. Future Oncol. 2022 Jun;18(17):2053-2062. doi: 10.2217/fon-2021-1342. Epub 2022 Mar 31.