Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults With Epithelial Cancer

NCT ID: NCT01631552

Last Updated: 2021-08-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

515 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-17

Study Completion Date

2020-08-13

Brief Summary

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The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day treatment cycles in previously treated participants with advanced epithelial cancer. In Phase II, the primary objective is to evaluate the safety and efficacy of sacituzumab govitecan-hziy administered in 21-day treatment cycles at a dose selected in Phase I.

Tumor types in the study will include: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC).

Detailed Description

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The outcome measures are planned to be assessed up to the data cutoff date. Following the data cutoff date, the participants will either stay on the study and will be followed for safety data collection or rolled into another Gilead-sponsored study. Therefore, only safety data will be collected after the data cutoff date.

Conditions

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Gastric Adenocarcinoma Esophageal Cancer Hepatocellular Carcinoma Non-small Cell Lung Cancer Small Cell Lung Cancer Ovarian Epithelial Cancer Carcinoma Breast Stage IV Hormone-refractory Prostate Cancer Head and Neck Cancers- Squamous Cell Renal Cell Cancer Urinary Bladder Neoplasms Cervical Cancer Endometrial Cancer Glioblastoma Multiforme Triple Negative Breast Cancer Pancreatic Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sacituzumab Govitecan-hziy (SG) 8 mg/kg

Participants will receive sacituzumab govitecan-hziy (SG) 8 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Sacituzumab Govitecan-hziy (SG)

Intervention Type DRUG

Administered via intravenous (IV) infusion

SG 10 mg/kg

Participants will receive SG 10 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Sacituzumab Govitecan-hziy (SG)

Intervention Type DRUG

Administered via intravenous (IV) infusion

SG 12 mg/kg

Participants will receive SG 12 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Sacituzumab Govitecan-hziy (SG)

Intervention Type DRUG

Administered via intravenous (IV) infusion

SG 18 mg/kg

Participants will receive SG 18 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Sacituzumab Govitecan-hziy (SG)

Intervention Type DRUG

Administered via intravenous (IV) infusion

Interventions

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Sacituzumab Govitecan-hziy (SG)

Administered via intravenous (IV) infusion

Intervention Type DRUG

Other Intervention Names

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hRS7-SN38 IMMU-132

Eligibility Criteria

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Inclusion Criteria

* Individuals able to understand and give written informed consent.
* Histologically or cytologically confirmed epithelial cancer of one of the following types:

* Gastric adenocarcinoma (GC)
* Esophageal cancer (EC)
* Hepatocellular carcinoma (HCC)
* Non-small-cell lung cancer (NSCLC)
* Small-cell lung cancer (SCLC)
* Epithelial ovarian cancer (EOC)
* Cervical Cancer
* Endometrial Cancer
* Triple-negative breast cancer (TNBC)
* Non-triple-negative breast cancer
* Papillary thyroid cancer (excludes follicular, medullary, Hurthle cell, and anaplastic thyroid cancer)
* Glioblastoma multiforme (GBM)
* Hormone-refractory prostate cancer (HRPC)
* Head and neck cancers- squamous cell (SCCHN)
* Renal cell cancer (clear cell) (RCC)
* Urothelial cancer
* Stage IV (metastatic) disease (except for individuals with GBM).
* Refractory to or relapsed after at least one prior standard therapeutic regimen
* Adequate performance status (ECOG 0 or 1)
* Expected survival ≥ 6 months.
* Measurable disease by CT or MRI.
* At least 2 weeks beyond treatment (chemotherapy, investigational drugs including small molecular inhibitors, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities to Grade 1 or less (except alopecia).
* At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids \< 20 mg prednisone or equivalent daily are permitted).
* Adequate hematology without ongoing transfusional support (hemoglobin \> 9 g/dL, absolute neutrophil count (ANC) \> 1,500 per mm\^3, platelets \> 100,000 per mm\^3).
* Adequate renal and hepatic function (creatinine ≤ 2.0 x institutional upper limit of normal (IULN), bilirubin ≤ 1.5 IULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x IULN or 5 x IULN if know liver metastases).
* Otherwise, all toxicity at study entry ≤ Grade 1.

Exclusion Criteria

* Women who are pregnant or lactating.
* Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.
* Individuals with Gilbert's disease.
* Individuals with brain metastases can be enrolled only if treated, non-progressive brain metastases and off high-dose steroids (\> 20 mg prednisone or equivalent) for at least 4 weeks.
* Presence of bulky disease (defined as any single mass \> 7 cm in its greatest dimension). Individuals with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor.
* Individuals with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
* Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while individuals with other prior malignancies must have had at least a 3-year disease-free interval.
* Individuals known to be HIV positive, hepatitis B positive, or hepatitis C positive.
* Known history of unstable angina, MI, or CHF present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
* Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.
* Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of initiation of study treatment.
* Infection requiring intravenous antibiotic use within 1 week.
* History of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior irinotecan,
* Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

Helen F. Graham Cancer Center

Newark, Delaware, United States

Site Status

MD Anderson Cancer Center Orlando (UF Health Cancer Center)

Orlando, Florida, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

IU Health Goshen Cancer Center

Goshen, Indiana, United States

Site Status

Massachusettes General Hospital

Boston, Massachusetts, United States

Site Status

Weill Cornell/New York Presbyterian Hospital

New York, New York, United States

Site Status

Columbia University Herbert Irving Cancer Center

New York, New York, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Oncology Sammons Cancer Center

Dallas, Texas, United States

Site Status

Virginia Mason Cancer Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O'Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldenberg DM, Sharkey RM, Maliakal P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020 Dec;31(12):1709-1718. doi: 10.1016/j.annonc.2020.09.004. Epub 2020 Sep 15.

Reference Type RESULT
PMID: 32946924 (View on PubMed)

Santin AD, Komiya T, Goldenberg DM, et al. Sacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase 1/2 study. J Clin Oncol. 2020; 38 (suppl; abstr 6081)

Reference Type RESULT

Bardia A, Mayer IA, Kalinsky K. Sacituzumab Govitecan-hziy in Triple-Negative Breast Cancer. Reply. N Engl J Med. 2019 Jun 13;380(24):2382. doi: 10.1056/NEJMc1903943. No abstract available.

Reference Type RESULT
PMID: 31189049 (View on PubMed)

Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O'Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2019 Feb 21;380(8):741-751. doi: 10.1056/NEJMoa1814213.

Reference Type RESULT
PMID: 30786188 (View on PubMed)

Tagawa ST, Faltas M, Lam ET, et al. Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study. J Clin Oncol. 2019;39(suppl 7S):abstr 354.

Reference Type RESULT

Bardia A, Diamond JR, Vahdat LT, et al. Efficacy of sacituzumab govitecan (anti-Trop-2-SN-38 antibody-drug conjugate) for treatment-refractory hormone-receptor positive (HR+)/HER2- metastatic breast cancer (mBC). J Clin Oncol. 2018;36(15 suppl):1004.

Reference Type RESULT

Gray JE, Heist RS, Starodub AN, Camidge DR, Kio EA, Masters GA, Purcell WT, Guarino MJ, Misleh J, Schneider CJ, Schneider BJ, Ocean A, Johnson T, Gandhi L, Kalinsky K, Scheff R, Messersmith WA, Govindan SV, Maliakal PP, Mudenda B, Wegener WA, Sharkey RM, Goldenberg DM. Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Clin Cancer Res. 2017 Oct 1;23(19):5711-5719. doi: 10.1158/1078-0432.CCR-17-0933. Epub 2017 Jul 5.

Reference Type RESULT
PMID: 28679770 (View on PubMed)

Ocean AJ, Starodub AN, Bardia A, Vahdat LT, Isakoff SJ, Guarino M, Messersmith WA, Picozzi VJ, Mayer IA, Wegener WA, Maliakal P, Govindan SV, Sharkey RM, Goldenberg DM. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Cancer. 2017 Oct 1;123(19):3843-3854. doi: 10.1002/cncr.30789. Epub 2017 May 30.

Reference Type RESULT
PMID: 28558150 (View on PubMed)

Heist RS, Guarino MJ, Masters G, Purcell WT, Starodub AN, Horn L, Scheff RJ, Bardia A, Messersmith WA, Berlin J, Ocean AJ, Govindan SV, Maliakal P, Mudenda B, Wegener WA, Sharkey RM, Goldenberg DM, Camidge DR. Therapy of Advanced Non-Small-Cell Lung Cancer With an SN-38-Anti-Trop-2 Drug Conjugate, Sacituzumab Govitecan. J Clin Oncol. 2017 Aug 20;35(24):2790-2797. doi: 10.1200/JCO.2016.72.1894. Epub 2017 May 26.

Reference Type RESULT
PMID: 28548889 (View on PubMed)

Bardia A, Mayer IA, Diamond JR, Moroose RL, Isakoff SJ, Starodub AN, Shah NC, O'Shaughnessy J, Kalinsky K, Guarino M, Abramson V, Juric D, Tolaney SM, Berlin J, Messersmith WA, Ocean AJ, Wegener WA, Maliakal P, Sharkey RM, Govindan SV, Goldenberg DM, Vahdat LT. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017 Jul 1;35(19):2141-2148. doi: 10.1200/JCO.2016.70.8297. Epub 2017 Mar 14.

Reference Type RESULT
PMID: 28291390 (View on PubMed)

Sharkey RM, McBride WJ, Cardillo TM, Govindan SV, Wang Y, Rossi EA, Chang CH, Goldenberg DM. Enhanced Delivery of SN-38 to Human Tumor Xenografts with an Anti-Trop-2-SN-38 Antibody Conjugate (Sacituzumab Govitecan). Clin Cancer Res. 2015 Nov 15;21(22):5131-8. doi: 10.1158/1078-0432.CCR-15-0670. Epub 2015 Jun 23.

Reference Type RESULT
PMID: 26106073 (View on PubMed)

Starodub AN, Ocean AJ, Shah MA, Guarino MJ, Picozzi VJ Jr, Vahdat LT, Thomas SS, Govindan SV, Maliakal PP, Wegener WA, Hamburger SA, Sharkey RM, Goldenberg DM. First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Clin Cancer Res. 2015 Sep 1;21(17):3870-8. doi: 10.1158/1078-0432.CCR-14-3321. Epub 2015 May 5.

Reference Type RESULT
PMID: 25944802 (View on PubMed)

Kwapisz D. Sacituzumab Govitecan-hziy in Breast Cancer. Am J Clin Oncol. 2022 Jul 1;45(7):279-285. doi: 10.1097/COC.0000000000000919. Epub 2022 May 12.

Reference Type DERIVED
PMID: 35728046 (View on PubMed)

Bardia A, Messersmith WA, Kio EA, Berlin JD, Vahdat L, Masters GA, Moroose R, Santin AD, Kalinsky K, Picozzi V, O'Shaughnessy J, Gray JE, Komiya T, Lang JM, Chang JC, Starodub A, Goldenberg DM, Sharkey RM, Maliakal P, Hong Q, Wegener WA, Goswami T, Ocean AJ. 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. Ann Oncol. 2021 Jun;32(6):746-756. doi: 10.1016/j.annonc.2021.03.005. Epub 2021 Mar 16.

Reference Type DERIVED
PMID: 33741442 (View on PubMed)

Faltas B, Goldenberg DM, Ocean AJ, Govindan SV, Wilhelm F, Sharkey RM, Hajdenberg J, Hodes G, Nanus DM, Tagawa ST. Sacituzumab Govitecan, a Novel Antibody--Drug Conjugate, in Patients With Metastatic Platinum-Resistant Urothelial Carcinoma. Clin Genitourin Cancer. 2016 Feb;14(1):e75-9. doi: 10.1016/j.clgc.2015.10.002. Epub 2015 Oct 19.

Reference Type DERIVED
PMID: 26541586 (View on PubMed)

Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Arrojo R, Liu D, Rossi EA, Chang CH, Goldenberg DM. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Bioconjug Chem. 2015 May 20;26(5):919-31. doi: 10.1021/acs.bioconjchem.5b00223. Epub 2015 May 8.

Reference Type DERIVED
PMID: 25915780 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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IMMU-132-01

Identifier Type: -

Identifier Source: org_study_id

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