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Avelumab/kg Q2W

Phase 1

Metastatic Solid Tumors | Small molecule | Oncology |Merck KGaA|Last Updated: Feb 23, 2024

Target and mechanism

Molecular targetCD274
Target classOther
ModalitySmall molecule

Also known as Avelumab, Avelumab Injection

Success Probability

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Market & Valuation

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Trial Design

CONTROLLEDDMC
Total Trials1
Total Enrollment24

FDA Designations

No designations recorded

Clinical trial landscape

Avelumab/kg Q2W · 1 trial · 1 indication

Phase 1 1
NCT03523390Phase I/Ib Multiple Ascending Dose Study in ChinaMetastatic Solid Tumors
COMPLETED24 Analytics
PHASE1COMPLETED
Phase I/Ib Multiple Ascending Dose Study in China
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Study Endpoints

Primary Endpoints

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
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
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
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
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
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
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
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
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
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
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
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
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
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.

Secondary Endpoints

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 from first study treatment up to 139 weeks
Number of Participants With at Least 1 Positive Anti-Avelumab Antibodies (ADA)
Time from first study treatment up to 139 weeks
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Avelumab 3 mg/kg Q2WEXPERIMENTAL -
Avelumab 10 mg/kg Q2WEXPERIMENTAL -
Avelumab 20 mg/kg Q2WEXPERIMENTAL -
Avelumab 10 mg/kg QWEXPERIMENTAL -

Interventions

NameTypeDescription
Avelumab 3 mg/kg Q2WDRUGParticipants 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 Q2WDRUGParticipants 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 Q2WDRUGParticipants 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 QWDRUGParticipants 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.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites3

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 stan...

Countries:China
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Competitive Landscape -Other Solid Tumors 9 trials (matched to "Metastatic Solid Tumors")

Frequently asked questions about Avelumab/kg Q2W

What is Avelumab used for?

Avelumab is an investigational antibody being studied for several cancers, including unresectable, locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction, gestational trophoblastic neoplasias, non-Hodgkin's B-cell lymphomas, non-metastatic muscle invasive bladder cancer, and squamous cell carcinoma of the head and neck. It is also being studied in treatment-related cancer.

What does Avelumab target?

Avelumab is a monoclonal antibody, classified as a -mab (antibody) therapeutic. As an antibody, it is designed to bind to specific targets on cells, though its precise molecular target is not detailed here. It is being evaluated in multiple cancer types for its potential anti-tumor activity.

Who is developing Avelumab?

Avelumab is being developed by Merck KGaA, a biopharmaceutical company. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various cancer indications. Merck KGaA's ticker symbol is MKGAF.

What phase is Avelumab in?

Avelumab is in Phase 1 clinical development. While some completed trials have been conducted, the drug remains investigational and has not been approved by regulatory authorities. It is being studied across multiple phases, including Phase 1, Phase 2, and Phase 3 trials, but the overall development stage is Phase 1.

What clinical trials is Avelumab in?

Avelumab is being studied in several clinical trials, including NCT02625610, a Phase 3 trial in gastric cancer with 499 participants, and NCT03244176, an early Phase 1 trial in non-Hodgkin's B-cell lymphomas. Other trials include NCT03523390 in China and NCT05217069 in colorectal cancer.

Is Avelumab the same as Avelumab Injection?

Yes, Avelumab is also known as Avelumab Injection. This alternative name refers to the same drug product, which is administered via injection. Researchers and clinicians may use either name when referring to this investigational antibody therapy.