First-in-Human Phase I Study of ABBV-085, an Antibody-Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors.

Autor:	Demetri GD; Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute; Ludwig Center at Harvard, Harvard Medical School, Boston, Massachusetts. gdemetri@dfci.harvard.edu., Luke JJ; Department of Medicine, The University of Chicago, Chicago, Illinois., Hollebecque A; Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France., Powderly JD 2nd; Carolina BioOncology Institute, Huntersville, North Carolina., Spira AI; Virginia Cancer Specialists, Fairfax, Virginia., Subbiah V; Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas., Naumovski L; Oncology Early Development, AbbVie Inc., Redwood City, California., Chen C; Oncology Early Development, AbbVie Inc., Redwood City, California., Fang H; Oncology Early Development, AbbVie Inc., Redwood City, California., Lai DW; Oncology Early Development, AbbVie Inc., Redwood City, California., Yue H; Oncology Early Development, AbbVie Inc., Redwood City, California., Polepally AR; Oncology Early Development, AbbVie Inc., Redwood City, California., Purcell JW; Oncology Early Development, AbbVie Inc., Redwood City, California., Robinson R; Oncology Early Development, AbbVie Inc., Redwood City, California., Sharma P; Department of Immunology, MD Anderson Cancer Center, Houston, Texas., Allison JP; Department of Immunology, MD Anderson Cancer Center, Houston, Texas., Tolcher A; South Texas Accelerated Research Therapeutics (START), San Antonio, Texas., Villalobos VM; University of Colorado - Anschutz Medical Campus, Aurora, Colorado.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Jul 01; Vol. 27 (13), pp. 3556-3566. Date of Electronic Publication: 2021 Apr 05.
DOI:	10.1158/1078-0432.CCR-20-4513
Abstrakt:	Purpose: Leucine-rich repeat containing 15 (LRRC15) is expressed on stromal fibroblasts in the tumor microenvironment of multiple solid tumor types and may represent an interesting target for therapy, particularly in patients with sarcomas where LRRC15 is also expressed by malignant cells. ABBV-085 is a monomethyl auristatin-E antibody-drug conjugate that targets LRRC15 and showed antineoplastic efficacy in preclinical experiments. Herein, we report findings of ABBV-085 monotherapy or combination therapy in adult patients with sarcomas and other advanced solid tumors. Patients and Methods: This first-in-human phase I study (NCT02565758) assessed ABBV-085 safety, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity. The study consisted of two parts: dose escalation and dose expansion. ABBV-085 was administered by intravenous infusion at 0.3 to 6.0 mg/kg every 14 days. Results: In total, 85 patients were enrolled; 45 patients received the recommended expansion dose of 3.6 mg/kg ABBV-085 monotherapy, including 10 with osteosarcoma and 10 with undifferentiated pleomorphic sarcoma (UPS). Most common treatment-related adverse events were fatigue, nausea, and decreased appetite. The overall response rate for patients with osteosarcoma/UPS treated at 3.6 mg/kg was 20%, including four confirmed partial responses. No monotherapy responses were observed for other advanced cancers treated at 3.6 mg/kg. One patient treated with ABBV-085 plus gemcitabine achieved partial response. Conclusions: ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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