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Denlinger CS, Keedy VL, Moyo V, et al. Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Invest New Drugs. 2021;39(6):1604-1612doi: 10.1007/s10637-021-01145-y.
Denlinger, C. S., Keedy, V. L., Moyo, V., MacBeath, G., & Shapiro, G. I. (2021). Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Investigational new drugs, 39(6), 1604-1612. https://doi.org/10.1007/s10637-021-01145-y
Denlinger, Crystal S, et al. "Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors." Investigational new drugs vol. 39,6 (2021): 1604-1612. doi: https://doi.org/10.1007/s10637-021-01145-y
Denlinger CS, Keedy VL, Moyo V, MacBeath G, Shapiro GI. Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Invest New Drugs. 2021 Dec;39(6):1604-1612. doi: 10.1007/s10637-021-01145-y. Epub 2021 Jul 11. PMID: 34250553; PMCID: PMC8541959.
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Invest New Drugs. 2021 Dec;39(6):1604-1612. doi: 10.1007/s10637-021-01145-y. Epub 2021 Jul 11.

Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors.

Investigational new drugs

Crystal S Denlinger, Vicki L Keedy, Victor Moyo, Gavin MacBeath, Geoffrey I Shapiro

Affiliations

  1. Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. [email protected].
  2. Department of Medicine (Hematology and Oncology), Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
  3. Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA.
  4. Dana-Farber Cancer Institute, Boston, MA, USA.

PMID: 34250553 PMCID: PMC8541959 DOI: 10.1007/s10637-021-01145-y

Abstract

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, reported in 24% and 39% of patients during the dose escalation and expansion portions of the study, respectively. Seribantumab terminal half-life was ≈100 h; 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. August 12, 2008.

© 2021. The Author(s).

Keywords: Advanced solid tumor; Anti-HER3 mAb; Dose-escalation study; HER3; MM-121; Monoclonal antibody; Seribantumab

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