Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial

Abstract

Background: Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody-drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020.

Patients and methods: We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) HR+/HER2- mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety.

Results: Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%-45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7-12.7), median PFS was 5.5 months (95% CI 3.6-7.6), and median OS was 12 months (95% CI 9.0-18.2).

Conclusions: SG shows encouraging activity in patients with pretreated HR+/HER2- mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339).

Trial registration: ClinicalTrials.gov NCT01631552; https://ichgcp.net/clinical-trials-registry/NCT01631552.

Keywords: IMMU-132-01; SN-38; TROPiCS-02; Trop-2; antibody–drug conjugate.

Conflict of interest statement

Disclosure This study was sponsored by Immunomedics, Inc. KK reports serving as a consultant/advisory board member for Immunomedics, BioTheranostics, Pfizer, Novartis, Eisai, Eli Lilly, Amgen, and AstraZeneca; receiving institutional grants from Immunomedics, Novartis, Incyte, Genentech/Roche, Eli Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zentalis Pharmaceuticals, and CytomX Therapeutics; serving on speakers' bureau for Eli Lilly; receiving travel expenses from Lilly and Astra Zeneca; and that his spouse was previously employed by Novartis, Array Biopharma, and Pfizer. JRD reports receiving institutional grants from BMS, Taiho, MedImmune, Rexahn, Takeda, Merck, and Bayer and receiving travel expenses from MedImmune. LTV reports receiving institutional research funding from Novartis, Genentech/Roche, Eli Lilly, Pfizer, Merck, Eisai, Bristol-Myers Squibb, AstraZeneca, Immunomedics, Sanofi, Odonate, and Seattle Genetics and serving as a consultant/advisory board member for Seattle Genetics, Eisai, Berg Pharma, Osmol Therapeutics, and Celldex. SMT reports receiving institutional research funding from Novartis, Genentech/Roche, Eli Lilly, Pfizer, Merck, Exelixis, Eisai, Bristol-Myers Squibb, AstraZeneca, Cyclacel, Immunomedics, Sanofi, Odonate, and Nektar and serving as a paid advisor/consultant to Novartis, Athenex, Eli Lilly, Pfizer, Merck, AstraZeneca, Eisai, Puma, Genentech/Roche, Immunomedics, Nektar, Sanofi, Bristol-Myers Squibb, Tesaro, Outcomes4Me, and NanoString. DJ reports receiving clinical trial support from Immunomedics, Inc.; receiving institutional research funding from Novartis, Genentech, Eisai, EMD Serono, Takeda, Amgen, Celgene, Placon Therapeutics, Syros, Petra Pharma, InventisBio, and Infinity Pharmaceuticals; and receiving honoraria for serving as a consultant/advisory board member for Novartis, Genentech, Eisai, EMD Serono, Ipsen, Syros, Relay Therapeutics, MapKure, Vibliome, and Petra Pharma. JOS reports serving as a consultant/advisory board member for AstraZeneca, Novartis, Lilly, Pfizer, Merck, Genomic Health, Seattle Genetics, and Eisai Pharmaceuticals. RLM reports receiving clinical trial support from Immunomedics, Inc.; support for conducting the clinical trial from Orlando Health UF Health Cancer Center during the conduct of the study; and serving as a consultant/advisory board member for Eli Lilly, Pfizer, Genentech, Immunomedics, Seattle Genetics, and BMS. IAM reports receiving research grants from Pfizer, Genentech, and Novartis and serving as a consultant/advisory board member for Genentech, Novartis, Pfizer, Lilly, AstraZeneca, GSK, Puma, AbbVie, MacroGenics, and Seattle Genetics. VGA reports receiving research funding from Genentech and Lilly and serving as a consultant/advisory board member for Novartis, AstraZeneca, and AbbVie. RMS reports previous employment by Immunomedics, Inc. while the study was performed; serving as a paid consultant to Immunomedics, Inc.; and being a stockholder in Immunomedics, Inc. from prior employment. DMG reports previous employment by Immunomedics, Inc. and status as company founder while the study was performed; serving as Chairman of the Board and Chief Scientific Officer of Immunomedics, Inc. while the study was performed; being a stockholder in Immunomedics, Inc.; and invention of patents pertaining to SG. PM reports previous employment by Immunomedics, Inc. while the study was performed and being a stockholder in Immunomedics, Inc. QH reports employment by Immunomedics, Inc. and being a stockholder in Immunomedics, Inc. TG reports employment by Immunomedics, Inc. and being a stockholder in Immunomedics, Inc. WAW reports previous employment by Immunomedics, Inc. while the study was performed; serving as a consultant to Immunomedics, Inc.; and being a stockholder in Immunomedics, Inc. AB reports serving as a consultant/advisory board member for Immunomedics, Inc., Pfizer, Novartis, Genentech, Merck, Radius Health, Spectrum Pharma, and Taiho Pharma; receiving research grants from BioTheranostics, Inc. during the conduct of the study; and receiving institutional grants from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Inc., Mersana, and Innocrin.

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.