First-in-human phase I study of ABBV-085, an antibody–drug conjugate targeting LRRC15, in sarcomas and other advanced solid tumors

George D. Demetri, Jason J. Luke, Antoine Hollebecque, John D. Powderly, Alexander I. Spira, Vivek Subbiah, Louie Naumovski, Chris Chen, Hua Fang, Dominic W. Lai, Huibin Yue, Akshanth R. Polepally, James W. Purcell, Randy Robinson, Padmanee Sharma, James P. Allison, Anthony Tolcher, Victor M. Villalobos

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3556-3566
Number of pages11
JournalClinical Cancer Research
Volume27
Issue number13
DOIs
StatePublished - Jul 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'First-in-human phase I study of ABBV-085, an antibody–drug conjugate targeting LRRC15, in sarcomas and other advanced solid tumors'. Together they form a unique fingerprint.

Cite this