ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT)

• ClinicalTrials.gov Identifier: NCT02574455
• Recruitment Status: Completed
• First Posted: October 12, 2015
• Last Update Posted: December 8, 2020
• Sponsor: Immunomedics, Inc.
• Information provided by (Responsible Party): Immunomedics, Inc.

Tracking Information

• First Submitted Date: October 8, 2015
• First Posted Date: October 12, 2015
• Last Update Posted Date: December 8, 2020
• Actual Study Start Date: November 3, 2017
• Actual Primary Completion Date: March 11, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2015)

Progression-Free Survival (PFS): [ Time Frame: 3 YEARS ]

PFS

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 9, 2015)

• Overall Survival (OS): [ Time Frame: 3 YEARS ]
  OS will compared between the two treatment groups. PFS will be measured by an independent centralized and blinded group of radiology experts who will be assessing tumor response using RECIST 1.1 criteria. FDA definitions and guidance as described in Guidance for Industry:
• Objective Response Rate [ Time Frame: 3 years ]
  ORR will compared between the two treatment groups.
• Duration of Response [ Time Frame: 3 years ]
  Duration of response will compared between the two treatment groups.
• Time to Onset of response [ Time Frame: 3 years ]
  Time to onset of response will compared between the two treatment groups.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer
• Official Title: Phase III Study of Sacituzumab Govitecan (IMMU-132) in Refractory/Relapsed Triple-Negative Breast Cancer
• Brief Summary: This is an international, multi-center, open-label, randomized, Phase III study in patients with metastatic TNBC refractory or relapsing after at least 2 prior chemotherapies (including a taxane) for their metastatic disease. Patients meeting eligibility will be randomized 1:1 to receive either sacituzumab govitecan or treatment of physician choice (TPC) Patients will be treated until progression, unacceptable toxicity, study withdrawal, or death, whichever comes first. Tumor progression leading to treatment withdrawal will be assessed by the investigator. Starting with the initial dose of sacituzumab govitecan or TPC, Imaging assessments will be obtained at least every 6 weeks for 36 weeks, then every 9 weeks thereafter until the occurrence of progression of disease requiring discontinuation of further treatment. All patients will be followed every 4 weeks for survival follow-up.

Detailed Description

This is an international, multi-center, open-label, randomized, Phase III study in patients with metastatic TNBC refractory or relapsing after at least 2 prior chemotherapies (including a taxane) for their metastatic disease.

The primary objective of this study is to compare the efficacy of sacituzumab govitecan to the treatment of physician's choice (TPC) as measured by progression-free survival (PFS) in patients with metastatic TNBC previously treated with at least two systemic chemotherapy regimens.

The secondary objectives of the study are to compare between the two treatment groups for:

• Overall Survival (OS)
• Independently-determined Objective Response Rate (ORR), duration of response and time to onset of response per RECIST 1.1 criteria
• Quality of life
• Safety (adverse events, safety laboratories, incidence of dose delays and dose reductions, treatment discontinuations due to adverse events)
• Exploratory objectives include exposure-response analysis for the efficacy (PFS and OS) and safety (incidence of Grade 3-5 adverse events, related to UGT1A1 endpoints).

Four-Hundred and eighty-eight patients are anticipated to be enrolled. Approximately 150 institutions will participate in this study, including sites in North America and Europe.

Clinical sites will use standard ASCO/CAP criteria for the pathological diagnosis of TNBC, defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Receptor results will be based on local assessment.

BRCA 1&2 mutational status will be collected, if known. A single whole-blood sample will be also collected from all patients for determination of UGT1A1 genotype for retrospective assessment predicting of toxicity.

The Sponsor will request slides from prior (archived) biopsy or surgical specimens, particularly for immunohistology documentation of tumor Trop-2 expression and other appropriate tumor markers.

Patients meeting eligibility will be randomized 1:1 to receive either sacituzumab govitecan or treatment of physician choice (TPC), which needs to be selected prior to randomization from one of the 4 allowed regimens. Randomization will be stratified by number of prior chemotherapies for advanced disease (2-3 vs > 3) and geographical location (North America vs Europe) and known brain metastasis at baseline (yes or no).

Patients will be treated until progression, unacceptable toxicity, study withdrawal, or death, whichever comes first. Tumor progression leading to treatment withdrawal will be assessed by the investigator.

No crossover to sacituzumab govitecan treatment will be allowed after discontinuing treatment in the TPC arm, but otherwise there is no restriction on subsequent therapies that a patient may receive after discontinuing the study.

All patients, including those prematurely terminating study participation, will be followed every 4 weeks for survival follow-up.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Sacituzumab govitecan
  Sacituzumab govitecan (10 mg/kg on Days 1 and 8 of 21-day cycles)
  Other Name: IMMU-132
• Drug: Eribulin
  Eribulin (1.4 mg/m2 IV on Days 1 and 8 of a 21-day cycle) See section 6.5.1
  Other Name: Halaven
• Drug: Capecitabine
  Capecitabine (1000-1250 mg/m2 orally twice daily on Days 1-14 of a 21-day cycle) See section 6.5.2
  Other Name: Xeloda
• Drug: Gemcitabine
  Gemcitabine (800-1200 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle). See section 6.5.3
  Other Name: Gemzar
• Drug: Vinorelbine
  Vinorelbine (25 mg/m2 IV on Day 1 weekly). See section 6.5.4 (Note: eligible patients with Grade 2 neuropathy should not be prescribed vinorelbine as TPC).
  Other Name: Navelbine

Study Arms

• Experimental: IMMU-132
  Sacituzumab govitecan (10 mg/kg on Days 1 and 8 of 21-day cycles)
  Intervention: Drug: Sacituzumab govitecan
• Active Comparator: Control Arm

  Treatment of Physician's Choice determined before randomization from only one of the following treatments (see Appendix 2 for more details on administration and dosing management):

  Eribulin (1.4 mg/m2 IV on Days 1 and 8 of a 21-day cycle). See section 6.5.1 Capecitabine (1000-1250 mg/m2 orally twice daily on Days1-14 of a 21-day cycle). See section 6.5.2 Gemcitabine (800-1200 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle). See section 6.5.3 Vinorelbine (25 mg/m2 weekly IV on Day 1 weekly) See section 6.5.4 (Note: eligible patients with Grade 2 neuropathy should not be prescribed vinorelbine as TPC)

  Interventions:

  • Drug: Eribulin
  • Drug: Capecitabine
  • Drug: Gemcitabine
  • Drug: Vinorelbine

Publications *

• 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.
• Seligson JM, Patron AM, Berger MJ, Harvey RD, Seligson ND. Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Ann Pharmacother. 2020 Oct 17:1060028020966548. doi: 10.1177/1060028020966548. [Epub ahead of print]

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 19, 2019): 529
• Original Estimated Enrollment (submitted: October 9, 2015): 328
• Actual Study Completion Date: December 3, 2020
• Actual Primary Completion Date: March 11, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Female or male patients, ≥18 years of age, able to understand and give written informed consent.
• Histologically or cytologically confirmed TNBC based on the most recent analyzed biopsy or other pathology specimen. Triple negative defined as <1% expression for estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2) by in-situ hybridization.
• Refractory to or relapsed after at least two prior standard therapeutic regimens for advanced/metastatic TNBC.
• Prior exposure to a taxane in localized or advanced/metastatic setting.
• Eligible for one of the chemotherapy options listed as TPC (Eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment.
• ECOG performance score of 0 or 1 .
• Measurable disease by CT or MRI as per RECIST 1.1. Bone-only disease is not permitted.
• At least 2 weeks beyond prior anti-cancer treatment (chemotherapy, endocrine therapy, radiotherapy, and/or major surgery), and recovered from all acute toxicities to Grade 1 or less (except alopecia and peripheral neuropathy).
• 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, ANC > 1,500 per mm3, platelets > 100,000 per mm3).
• Adequate renal and hepatic function (CrCL> 60 mL/min, bilirubin ≤ 1.5 IULN, AST and ALT ≤ 2.5 x IULN or ≤ 5 x IULN if known liver metastases).
• Otherwise, all toxicity at study entry < Grade 1 by NCI CTCAE v4.03 (Patients with ≤ Grade 2 neuropathy are eligible).
• Patients with treated, non-progressive brain metastases, off high-dose steroids (>20 mg prednisone or equivalent) for at least 4 weeks can be enrolled in the trial.

Exclusion Criteria:

• Women who are pregnant or lactating.
• Women of childbearing potential or fertile men unwilling to use effective contraception during study and up to three months after treatment discontinuation in women of child-bearing potential and six months in males post last study drug.
• Patients with Gilbert's disease.
• Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while patients with other prior malignancies must have had at least a 3-year disease-free interval.
• Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
• Infection requiring antibiotic use within one week of randomization.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, France, Germany, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT02574455
• Other Study ID Numbers: IMMU-132-05
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Immunomedics, Inc.
• Study Sponsor: Immunomedics, Inc.
• Collaborators: Not Provided

Investigators

• Study Chair: Aditya Bardia, MD; Massachusetts General Hospital

• PRS Account: Immunomedics, Inc.
• Verification Date: December 2020