PMID- 33741442
OWN - NLM
STAT- MEDLINE
DCOM- 20210524
LR  - 20210524
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 32
IP  - 6
DP  - 2021 Jun
TI  - Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients 
      with epithelial cancer: final safety and efficacy results from the phase I/II 
      IMMU-132-01 basket trial.
PG  - 746-756
LID - S0923-7534(21)00883-8 [pii]
LID - 10.1016/j.annonc.2021.03.005 [doi]
AB  - BACKGROUND: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 
      (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy 
      and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in 
      patients with advanced epithelial cancers. This report summarizes the safety data 
      from the overall safety population (OSP) and efficacy data, including additional 
      disease cohorts not published previously. PATIENTS AND METHODS: Patients with 
      refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 
      18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or 
      unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic 
      parameters with investigator-evaluated objective response rate (ORR per RECIST 
      1.1), duration of response, clinical benefit rate, progression-free survival, and 
      overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, 
      colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and 
      castrate-resistant prostate cancer. RESULTS: In the OSP (n = 495, median age 61 
      years, 68% female; UGT1A1 *28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently 
      discontinued treatment due to adverse events (AEs). Most common treatment-related 
      AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and 
      neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) 
      were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade >/=3 neutropenia and 
      febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. 
      Neutropenia (all grades) was numerically more frequent in UGT1A1 *28 homozygotes 
      (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1 *1 wild type (59/177; 
      33.3%). There was one treatment-related death due to an AE of aspiration 
      pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) 
      and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant 
      prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). 
      CONCLUSIONS: SG demonstrated a toxicity profile consistent with previous 
      published reports. Efficacy was seen in several cancer cohorts, which validates 
      Trop-2 as a broad target in solid tumors.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Bardia, A
AU  - Bardia A
AD  - Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, 
      USA.
FAU - Messersmith, W A
AU  - Messersmith WA
AD  - University of Colorado Cancer Center, Aurora, USA.
FAU - Kio, E A
AU  - Kio EA
AD  - Goshen Center for Cancer Care, Goshen, USA.
FAU - Berlin, J D
AU  - Berlin JD
AD  - Vanderbilt-Ingram Cancer Center, Nashville, USA.
FAU - Vahdat, L
AU  - Vahdat L
AD  - Weill Cornell Medicine, New York, USA.
FAU - Masters, G A
AU  - Masters GA
AD  - Helen F Graham Cancer Center and Research Institute, Newark, USA.
FAU - Moroose, R
AU  - Moroose R
AD  - Orlando Health UF Health Cancer Center, Orlando, USA.
FAU - Santin, A D
AU  - Santin AD
AD  - Yale University School of Medicine, New Haven, USA.
FAU - Kalinsky, K
AU  - Kalinsky K
AD  - Columbia University Irving Medical Center-Herbert Irving Comprehensive Cancer 
      Center, New York, USA.
FAU - Picozzi, V
AU  - Picozzi V
AD  - Virginia Mason Cancer Center, Seattle, USA.
FAU - O'Shaughnessy, J
AU  - O'Shaughnessy J
AD  - Texas Oncology, Baylor University Medical Center, US Oncology, Dallas, USA.
FAU - Gray, J E
AU  - Gray JE
AD  - H. Lee Moffitt Cancer Center & Research Institute, Tampa, USA.
FAU - Komiya, T
AU  - Komiya T
AD  - Parkview Cancer Institute, Fort Wayne, USA.
FAU - Lang, J M
AU  - Lang JM
AD  - University of Wisconsin Carbone Cancer Center, Madison, USA.
FAU - Chang, J C
AU  - Chang JC
AD  - Houston Methodist Cancer Center, Houston, USA.
FAU - Starodub, A
AU  - Starodub A
AD  - Riverside Peninsula Cancer Institute, Newport News, USA.
FAU - Goldenberg, D M
AU  - Goldenberg DM
AD  - Immunomedics, Inc., a Subsidiary of Gilead Sciences, Inc., Morris Plains, USA.
FAU - Sharkey, R M
AU  - Sharkey RM
AD  - Immunomedics, Inc., a Subsidiary of Gilead Sciences, Inc., Morris Plains, USA.
FAU - Maliakal, P
AU  - Maliakal P
AD  - Immunomedics, Inc., a Subsidiary of Gilead Sciences, Inc., Morris Plains, USA.
FAU - Hong, Q
AU  - Hong Q
AD  - Immunomedics, Inc., a Subsidiary of Gilead Sciences, Inc., Morris Plains, USA.
FAU - Wegener, W A
AU  - Wegener WA
AD  - Immunomedics, Inc., a Subsidiary of Gilead Sciences, Inc., Morris Plains, USA.
FAU - Goswami, T
AU  - Goswami T
AD  - Immunomedics, Inc., a Subsidiary of Gilead Sciences, Inc., Morris Plains, USA.
FAU - Ocean, A J
AU  - Ocean AJ
AD  - Weill Cornell Medicine, New York, USA. Electronic address: 
      ajo9001@med.cornell.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT01631552
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210316
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunoconjugates)
RN  - M9BYU8XDQ6 (sacituzumab govitecan)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized
MH  - Camptothecin/analogs & derivatives
MH  - Female
MH  - Humans
MH  - *Immunoconjugates
MH  - *Lung Neoplasms
MH  - Male
MH  - Middle Aged
OTO - NOTNLM
OT  - IMMU-132
OT  - SN-38
OT  - Trop-2
OT  - antibody-drug conjugate
OT  - colorectal cancer
OT  - endometrial cancer
OT  - small-cell lung cancer
COIS- Disclosure AB has received research support (paid to institution) from Genentech, 
      Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Inc., Mersana, 
      Innocrin, and Biotheranostics Inc.; has served as a consultant to Biotheranostics 
      Inc., Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Inc., 
      Spectrum Pharma, Taiho, Sanofi, Daiichi Pharma/AstraZeneca, Puma, Philipps, and 
      Eli Lilly; and has received travel support from Biotheranostics Inc., Pfizer, 
      Novartis, Genentech, Merck, Radius Health, Immunomedics, Inc., Spectrum Pharma, 
      Taiho, Sanofi, and Philipps. WM has received research support (paid to 
      institution) from Immunomedics, Inc. EAK is a stockholder of Immunomedics, Inc. 
      JDB has received research support (paid to institution) from 
      AbbVie/Pharmacyclics, Beigene, EMD Serono, Immunomedics, Inc., Symphogen, Pfizer, 
      Taiho, Novartis, Genentech/Roche, Bayer, Lilly/Loxo, Incyte, Boston Biomedical, 
      Macrogenics, and I-Mab Biopharma; has served as a consultant to Ipsen, Clovis, 
      and QED Therapeutics, EMD Serono, Seattle Genetics, Bayer, Celgene, LSK 
      Biopharma, Eisai, AstraZeneca, Five Prime, Armo, AbbVie, Symphogen, Erytech, and 
      Gritstone; participates in a Data Safety Monitoring Board for the Pancreatic 
      Cancer Action Network; and receives compensation from the National Cancer 
      Institute for study sections and work on an Investigational Drug Steering 
      Committee. LV has received research support from Weill Cornell Medicine, serves 
      on advisory boards for Immunomedics, Inc., Berg Pharma, and Seattle Genetics, and 
      has served as a consultant to Osmol Therapeutics. RM has received research 
      support from the Orlando Health UF Health Cancer Center and has received 
      honorarium from Eli Lilly, Pfizer, Genentech, Immunomedics, Inc., Seattle 
      Genetics, and Bristol-Myers Squibb (BMS). ADS has served as a consultant to Puma 
      and Merck, and has received research support from Gilead, Puma, Immunomedics, 
      Inc., Synthon, Boehringer-Ingelheim, Genentech, and Tesaro. KK has received 
      research support from Immunomedics, Inc., Novartis, Incyte, Genentech/Roche, Eli 
      Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zentalis 
      Pharmaceuticals, and CytomX Therapeutics; has served as a consultant to 
      Immunomedics, Inc., Merck, Seattle Genetics, Pfizer, Novartis, Eisai, Eli Lilly, 
      Amgen, and AstraZeneca. His spouse is currently employed by Grail and was 
      previously employed at Array and Pfizer. JO has served as a consultant to AbbVie, 
      Agendia, AstraZeneca, BMS, Celgene, Eisai, Genentech, Immunomedics, Inc., Jounce 
      Therapeutics, Lilly, Merck, Novartis, Pfizer, Puma, Roche, and Seattle Genetics. 
      JEG has received research support from BMS, Merck, AstraZeneca, Array, Boehringer 
      Ingelheim, and Genentech, and has served as a consultant to BMS, Merck, Inivata, 
      EMD Serono/Merck KGaA, AstraZeneca, Celgene, and Novartis. TK has received travel 
      support from Merck and has received honoraria from Boehringer Ingelheim. JML 
      holds equity interest in Salus Discovery, LLC. He has served as a consultant to 
      Janssen, Sanofi, Astellas, Pfizer, and Immunomedics, Inc. AS has served as a 
      consultant to Sandoz and Bayer and has received speaking honoraria from BMS. DMG 
      reports previous employment by Immunomedics, Inc. and status as company founder; 
      serving as Chairman of the Board and Chief Scientific Officer of Immunomedics, 
      Inc.; and was a stockholder. He is an inventor and co-inventor of patents 
      pertaining to sacituzumab govitecan, with potential royalties from product sales. 
      RMS was previously employed by Immunomedics, Inc., at the time this study was 
      conducted; has served as a consultant to Immunomedics, Inc.; and was a 
      stockholder of Immunomedics, Inc. PM reports previous employment by Immunomedics, 
      Inc., while study was performed and being a stockholder in Immunomedics, Inc. QH 
      was an employee and stock shareholder of Immunomedics, Inc., a subsidiary of 
      Gilead Sciences, Inc. and has received travel support from Advaxis; spouse is an 
      employee and stock shareholder of Merck. WW reports previous employment by 
      Immunomedics, Inc., while study was performed; served as a consultant to 
      Immunomedics, Inc., and was a stockholder in Immunomedics, Inc. TG was an 
      employee and stockholder of Immunomedics, Inc. a subsidiary of Gilead Sciences, 
      Inc. AJO has served in a consulting or advisory role for Immunomedics, Inc., 
      Celgene, Tyme Therapeutics, Array, Merck, BMS, ProStrakan, Novartis, Pfizer, Eli 
      Lilly, and Genentech; has served in Speaker's Bureau for Daiichi Sankyo; and has 
      received travel, accommodations, expenses from Daiichi Sankyo. All other authors 
      have declared no conflicts of interest.
EDAT- 2021/03/21 06:00
MHDA- 2021/05/25 06:00
CRDT- 2021/03/20 06:00
PHST- 2020/12/24 00:00 [received]
PHST- 2021/03/02 00:00 [revised]
PHST- 2021/03/06 00:00 [accepted]
PHST- 2021/03/21 06:00 [pubmed]
PHST- 2021/05/25 06:00 [medline]
PHST- 2021/03/20 06:00 [entrez]
AID - S0923-7534(21)00883-8 [pii]
AID - 10.1016/j.annonc.2021.03.005 [doi]
PST - ppublish
SO  - Ann Oncol. 2021 Jun;32(6):746-756. doi: 10.1016/j.annonc.2021.03.005. Epub 2021 
      Mar 16.