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

NCT01631552 | Completed Phase 1 Results FDA Drug

• 1 other identifier: IMMU-132-01
• Study Type: interventional
• Target: 515
• Locations: 1 country
• Sites: 12

Brief Summary

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).

Conditions

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

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events

  Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.03. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population.

  First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) plus 30 days

• Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death

  Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).

  First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)

• Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events

  Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).

  First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)

• Objective Response Rate (ORR) by Independent Central Review (ICR)

  ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by ICR assessment according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.

  Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

• Objective Response Rate by Local Assessment

  ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by local assessment. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥3 0% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by Local Assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.

  Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Secondary Outcomes (12)

• Duration of Response by ICR

  Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

• Duration of Response by Local Assessment

  Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

• Time to Response by ICR

  Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

• Time to Response by Local Assessments

  Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

• Clinical Benefit Rate (CBR) by Local Assessment

  Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Study Arms (4)

Sacituzumab Govitecan-hziy (SG) 8 mg/kg

EXPERIMENTAL

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.

Drug: Sacituzumab Govitecan-hziy (SG)

SG 10 mg/kg

EXPERIMENTAL

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.

Drug: Sacituzumab Govitecan-hziy (SG)

SG 12 mg/kg

EXPERIMENTAL

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.

Drug: Sacituzumab Govitecan-hziy (SG)

SG 18 mg/kg

EXPERIMENTAL

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.

Drug: Sacituzumab Govitecan-hziy (SG)

Interventions

Sacituzumab Govitecan-hziy (SG) DRUG

Administered via intravenous (IV) infusion

Also known as: hRS7-SN38, IMMU-132

SG 10 mg/kg; SG 12 mg/kg; SG 18 mg/kg; Sacituzumab Govitecan-hziy (SG) 8 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (12)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 080045, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

Location

Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States

Location

MD Anderson Cancer Center Orlando (UF Health Cancer Center)

Orlando, Florida, 32806, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

IU Health Goshen Cancer Center

Goshen, Indiana, 46526, United States

Location

Massachusettes General Hospital

Boston, Massachusetts, 02114, United States

Location

Weill Cornell/New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Columbia University Herbert Irving Cancer Center

New York, New York, 10032, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37212, United States

Location

Texas Oncology Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Virginia Mason Cancer Center

Seattle, Washington, 98111, United States

Location

Related Publications (16)

• 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.

  PMID: 32946924 RESULT

• 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)

  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.

  PMID: 31189049 RESULT

• 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.

  PMID: 30786188 RESULT

• 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.

  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.

  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.

  PMID: 28679770 RESULT

• 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.

  PMID: 28558150 RESULT

• 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.

  PMID: 28548889 RESULT

• 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.

  PMID: 28291390 RESULT

• 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.

  PMID: 26106073 RESULT

• 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.

  PMID: 25944802 RESULT

• 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.

  PMID: 35728046 DERIVED

• 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.

  PMID: 33741442 DERIVED

• 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.

  PMID: 26541586 DERIVED

• 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.

  PMID: 25915780 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Carcinoma, Ovarian Epithelial; Breast Neoplasms; Carcinoma, Renal Cell; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Glioblastoma; Triple Negative Breast Neoplasms; Pancreatic Neoplasms

Interventions

sacituzumab govitecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases; Uterine Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2012
• First Posted: June 29, 2012
• Study Start: December 17, 2012
• Primary Completion: March 1, 2019
• Study Completion: August 13, 2020
• Last Updated: August 12, 2021
• Results First Posted: April 6, 2021

Record last verified: 2021-08

Locations

US (12)