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Research Article
Crystal Denliger
Fox Chase Cancer Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5663-7751
License:
This work is licensed under a CC BY 4.0 License. Read Full License
BACKGROUND: Overactivation of human epidermal growth factor receptor 3 (HER3) triggers multiple intracellular pathways resulting in tumor cell survival. This Phase 1 study assessed the safety, efficacy, and pharmacokinetics (PK) of seribantumab, a fully human anti-HER3 monoclonal antibody.
METHODS: Adult patients with advanced or refractory solid tumors were treated in six dose cohorts of seribantumab: 3.2, 6, 10, 15, or 20 mg/kg weekly, or 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose (40/20 mg/kg) using a modified 3+3 dose escalation strategy with cohort expansion. Primary objectives were identification of a recommended Phase 2 dose (RP2D) and determination of objective response rate. Secondary objectives were assessment of safety, dose-limiting toxicities, and PK.
RESULTS: Forty-four patients (26 dose escalation; 18 dose expansion) were enrolled. Seribantumab monotherapy was well tolerated with most adverse events being transient and mild to moderate (grade 1 or 2) in severity; maximum tolerated dose was not reached. The highest dose, 40/20 mg/kg, was identified as RP2D. Best response was stable disease, achieved by 24% and 39% of patients during the dose escalation and expansion portions of the study, respectively. Seribantumab terminal half-life was ≈100 hours; steady state concentrations were reached after 3–4 weekly doses.
CONCLUSIONS: Seribantumab monotherapy was well tolerated across all dose levels. Safety and PK data from this study support further seribantumab investigations in genomically defined populations.
CLINICAL TRIAL REGISTRATION: NCT00734305.
DATE OF REGISTRATION: August 12, 2008.
Keywords
Seribantumab, MM-121, HER3, monoclonal antibody, anti-HER3 mAb, advanced solid tumor, dose-escalation study
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See the published version of this preprint at Investigational New Drugs.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Crystal Denliger
Fox Chase Cancer Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5663-7751
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Investigational New Drugs.
Version 1
Posted 24 May, 2021
No community comments so far
Editor assigned
On 03 May, 2021
First submitted
On 30 Apr, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Investigational New Drugs.
BACKGROUND: Overactivation of human epidermal growth factor receptor 3 (HER3) triggers multiple intracellular pathways resulting in tumor cell survival. This Phase 1 study assessed the safety, efficacy, and pharmacokinetics (PK) of seribantumab, a fully human anti-HER3 monoclonal antibody.
METHODS: Adult patients with advanced or refractory solid tumors were treated in six dose cohorts of seribantumab: 3.2, 6, 10, 15, or 20 mg/kg weekly, or 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose (40/20 mg/kg) using a modified 3+3 dose escalation strategy with cohort expansion. Primary objectives were identification of a recommended Phase 2 dose (RP2D) and determination of objective response rate. Secondary objectives were assessment of safety, dose-limiting toxicities, and PK.
RESULTS: Forty-four patients (26 dose escalation; 18 dose expansion) were enrolled. Seribantumab monotherapy was well tolerated with most adverse events being transient and mild to moderate (grade 1 or 2) in severity; maximum tolerated dose was not reached. The highest dose, 40/20 mg/kg, was identified as RP2D. Best response was stable disease, achieved by 24% and 39% of patients during the dose escalation and expansion portions of the study, respectively. Seribantumab terminal half-life was ≈100 hours; steady state concentrations were reached after 3–4 weekly doses.
CONCLUSIONS: Seribantumab monotherapy was well tolerated across all dose levels. Safety and PK data from this study support further seribantumab investigations in genomically defined populations.
CLINICAL TRIAL REGISTRATION: NCT00734305.
DATE OF REGISTRATION: August 12, 2008.
Figure 1
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