Metastatic Solid TumorsPhase 1NCT03523390
Phase I/Ib Multiple Ascending Dose Study in China
A Phase 1 study testing Avelumab 3 mg/kg Q2W, Avelumab 10 mg/kg Q2W and Avelumab 20 mg/kg Q2W in people with Metastatic Solid Tumors, run by Merck KGaA, Darmstadt, Germany at 3 sites in China.
Trial summary
The purpose of this study was to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of Avelumab monotherapy in Chinese subjects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Solid Tumors
- What is being tested?
- Avelumab 3 mg/kg Q2W, Avelumab 10 mg/kg Q2W and Avelumab 20 mg/kg Q2W
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesChina
- Study dates
- 24 Apr 2018to 8 Feb 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
3 sites in 1 country.
China3 sites
Research site
Changchun, Jilin
Research site
Guangzhou, Guangzhou
Research site
Hangzhou, Zhejiang
About this study
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)
The purpose of this study was to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of Avelumab monotherapy in Chinese subjects.
- Conditions
- Metastatic Solid Tumors
- Being tested
- Avelumab 3 mg/kg Q2W, Avelumab 10 mg/kg Q2W, Avelumab 20 mg/kg Q2W, Avelumab 10 mg/kg QW
- Keywords
- Metastatic Solid Tumors, Avelumab, MSB0010718C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avelumab 3 mg/kg Q2WDrug
Also called MSB0010718C
Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 3 milligrams per kilogram (mg/kg) once every 2 weeks (Q2W) until disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or from Avelumab occurs.
Avelumab 10 mg/kg Q2WDrug
Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg Q2W until disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or from Avelumab occurs.
Avelumab 20 mg/kg Q2WDrug
Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 20 mg/kg Q2W until disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or from Avelumab occurs.
Avelumab 10 mg/kg QWDrug
Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg every week (QW) for the first 12 weeks followed by once every 2 weeks, started at Week 13 until disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or from Avelumab occurs.
| Study group | Role | What they receive |
|---|---|---|
| Avelumab 3 mg/kg Q2W | Experimental | Not described Receives: Drug: Avelumab 3 mg/kg Q2W |
| Avelumab 10 mg/kg Q2W | Experimental | Not described Receives: Drug: Avelumab 10 mg/kg Q2W |
| Avelumab 20 mg/kg Q2W | Experimental | Not described Receives: Drug: Avelumab 20 mg/kg Q2W |
| Avelumab 10 mg/kg QW | Experimental | Not described Receives: Drug: Avelumab 10 mg/kg QW |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
DLT is defined as greater than or equal to [>=] Grade (Gr)3 Adverse drug reaction (ADR) according to NCI-CTCAE v4.03, occurring during DLT observation period of dose escalation cohorts. ADR: any AE suspected to be related to avelumab by Investigator and/Sponsor. Following events were not considered as DLT: Gr3 infusion-related reaction resolving within 6 hours and controlled with medical management. Transient (less than or equal to [<=] 6 hours) Gr3 flu-like symptoms/fever, controlled with medical management. Transient (<=24 hours) Gr3 fatigue, local reactions, headache, nausea, emesis, resolves to <= Gr1. Gr3 skin toxicity/Gr3 Liver function test increase that resolves to <= Grade 1 in < 7 days after medical management. Gr3 diarrhea, out-of-range laboratory values without any clinical correlate that resolves to <= Grade 1 within 7 days with adequate medical management; Tumor flare phenomenon defined as local pain, irritation, rash localized at sites of known or suspected tumor.
Measured: Day 1 to Day 21
Area Under the Serum Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Avelumab
Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log linear trapezoidal rule.
Measured: 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
Area Under the Serum Concentration-Time Curve During a Dosing Interval (AUCtau) of Avelumab
AUCtau was defined as area under the serum concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule.
Measured: 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
Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.
Measured: 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
Terminal Elimination Rate Constant (Lambda z) of Avelumab
Lambda z was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.
Measured: 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
Maximum Observed Serum Concentration (Cmax) of Avelumab
Cmax was obtained directly from the serum concentration versus time curve.
Measured: 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
Last Quantifiable Serum Concentration (Clast) of Avelumab
Clast is the last measurable serum concentration of Avelumab.
Measured: 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
Serum Trough Concentration Levels (Ctrough) of Avelumab
Ctrough is defined as the concentration observed immediately before next dosing.
Measured: Day 1: within 2 hours prior to 1 hour infusion
Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab
The time to reach the maximum observed serum concentration (tmax) was obtained directly from the concentration versus time curve.
Measured: 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
Apparent Terminal Half Life (t1/2) of Avelumab
Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. t1/2 was calculated as log2/ lambda z. Lambda z was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.
Measured: 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
Dose Normalized Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of Avelumab
AUC0-t/Dose was defined as area under the serum concentration versus time curve from time of dosing to the time of the last measurable concentration divided by dose. AUC0-t/Dose was measured in (microgram*hour per milliliter)/(milligram per kilogram) (mcg*h/mL)/(mg/kg).
Measured: 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
Dose Normalized Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau/Dose) of Avelumab
AUCtau/Dose was calculated by as dose normalized area under the serum concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule.
Measured: 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
Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Avelumab
Cmax/Dose was defined as maximum observed serum concentration divided by dose.
Measured: 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 (2)
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)
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events that emerge during treatment having been absent pre-treatment, or worsen relative to the pre-treatment state and with onset dates occurring within the first dosing day of study treatment until 30 days after the last dose of study treatment. TEAEs include both Serious TEAEs and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention.
Measured: Time from first study treatment up to 139 weeks
Number of Participants With at Least 1 Positive Anti-Avelumab Antibodies (ADA)
Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of antidrug antibodies (ADA). Number of participants with ADA positive results for Avelumab were reported.
Measured: Time from first study treatment up to 139 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2018
- Study start24 Apr 2018
- Primary completion29 Jul 2019
- Study completion8 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Subsequent cohorts of subjects treated at different dose levels in this study.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03523390
- Sponsor's protocol ID
- MS100070_0035
- Status last verified
- Jul 2023
- First submitted
- 1 May 2018
- Last updated
- 23 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35354274
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03523390
- Acronym / sponsor ID
- MS100070_0035
- Conditions
- Metastatic Solid Tumors
- Keywords
- Metastatic Solid Tumors, Avelumab, MSB0010718C
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 24 Apr 2018 (actual)
- Primary completion
- 29 Jul 2019 (actual)
- Study completion
- 8 Feb 2021 (actual)
- First posted
- 14 May 2018 (actual)
- Results
- Posted 23 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of Avelumab monotherapy in Chinese subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Subsequent cohorts of subjects treated at different dose levels in this study.
| Arm | Type | Receives |
|---|---|---|
| Avelumab 3 mg/kg Q2W | Experimental | Drug: Avelumab 3 mg/kg Q2W |
| Avelumab 10 mg/kg Q2W | Experimental | Drug: Avelumab 10 mg/kg Q2W |
| Avelumab 20 mg/kg Q2W | Experimental | Drug: Avelumab 20 mg/kg Q2W |
| Avelumab 10 mg/kg QW | Experimental | Drug: Avelumab 10 mg/kg QW |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Avelumab 3 mg/kg Q2WAlso: MSB0010718CParticipants received intravenous infusion of Avelumab over 1 hour duration at a dose of 3 milligrams per kilogram (mg/kg) once every 2 weeks (Q2W) until disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or from Avelumab occurs. | Drug | Avelumab 3 mg/kg Q2W |
| Avelumab 10 mg/kg Q2WParticipants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg Q2W until disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or from Avelumab occurs. | Drug | Avelumab 10 mg/kg Q2W |
| Avelumab 20 mg/kg Q2WParticipants received intravenous infusion of Avelumab over 1 hour duration at a dose of 20 mg/kg Q2W until disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or from Avelumab occurs. | Drug | Avelumab 20 mg/kg Q2W |
| Avelumab 10 mg/kg QWParticipants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg every week (QW) for the first 12 weeks followed by once every 2 weeks, started at Week 13 until disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or from Avelumab occurs. | Drug | Avelumab 10 mg/kg QW |
Primary outcome
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
Time frame: Day 1 to Day 21
DLT is defined as greater than or equal to [>=] Grade (Gr)3 Adverse drug reaction (ADR) according to NCI-CTCAE v4.03, occurring during DLT observation period of dose escalation cohorts. ADR: any AE suspected to be related to avelumab by Investigator and/Sponsor. Following events were not considered as DLT: Gr3 infusion-related reaction resolving within 6 hours and controlled with medical management. Transient (less than or equal to [<=] 6 hours) Gr3 flu-like symptoms/fever, controlled with medical management. Transient (<=24 hours) Gr3 fatigue, local reactions, headache, nausea, emesis, resolves to <= Gr1. Gr3 skin toxicity/Gr3 Liver function test increase that resolves to <= Grade 1 in < 7 days after medical management. Gr3 diarrhea, out-of-range laboratory values without any clinical correlate that resolves to <= Grade 1 within 7 days with adequate medical management; Tumor flare phenomenon defined as local pain, irritation, rash localized at sites of known or suspected tumor.
Area Under the Serum Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Avelumab
Time frame: 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
Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log linear trapezoidal rule.
Area Under the Serum Concentration-Time Curve During a Dosing Interval (AUCtau) of Avelumab
Time frame: 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
AUCtau was defined as area under the serum concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule.
Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab
Time frame: 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
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.
Terminal Elimination Rate Constant (Lambda z) of Avelumab
Time frame: 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
Lambda z was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.
Maximum Observed Serum Concentration (Cmax) of Avelumab
Time frame: 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
Cmax was obtained directly from the serum concentration versus time curve.
Last Quantifiable Serum Concentration (Clast) of Avelumab
Time frame: 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
Clast is the last measurable serum concentration of Avelumab.
Serum Trough Concentration Levels (Ctrough) of Avelumab
Time frame: Day 1: within 2 hours prior to 1 hour infusion
Ctrough is defined as the concentration observed immediately before next dosing.
Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab
Time frame: 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
The time to reach the maximum observed serum concentration (tmax) was obtained directly from the concentration versus time curve.
Apparent Terminal Half Life (t1/2) of Avelumab
Time frame: 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
Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination. t1/2 was calculated as log2/ lambda z. Lambda z was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.
Dose Normalized Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of Avelumab
Time frame: 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
AUC0-t/Dose was defined as area under the serum concentration versus time curve from time of dosing to the time of the last measurable concentration divided by dose. AUC0-t/Dose was measured in (microgram*hour per milliliter)/(milligram per kilogram) (mcg*h/mL)/(mg/kg).
Dose Normalized Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau/Dose) of Avelumab
Time frame: 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
AUCtau/Dose was calculated by as dose normalized area under the serum concentration-time curve from time zero to the end of the dosing interval (tau). AUCtau was calculated using the mixed log linear trapezoidal rule.
Dose Normalized Maximum Observed Serum Concentration (Cmax/Dose) of Avelumab
Time frame: 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
Cmax/Dose was defined as maximum observed serum concentration divided by dose.
2 secondary outcomes
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)
Time frame: Time from first study treatment up to 139 weeks
Number of Participants With at Least 1 Positive Anti-Avelumab Antibodies (ADA)
Time frame: Time from first study treatment up to 139 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 35354274Wu 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.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Avelumab 3 mg/kg Q2W, Avelumab 10 mg/kg Q2W and Avelumab 20 mg/kg Q2W in people with Metastatic Solid Tumors, run by Merck KGaA, Darmstadt, Germany at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Day 1 to Day 21). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03523390, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2024.