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Clin Cancer Res. 2015 Sep 1;21(17):3870-8. doi: 10.1158/1078-0432.CCR-14-3321. Epub 2015 May 5.

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors.

Author information

1
Indiana University Health Goshen Center for Cancer Care, Goshen, Indiana.
2
NewYork Presbyterian Hospital/Weill Cornell Medical Center, New York, New York.
3
Christiana Care Health System Graham Cancer Center, Newark, Delaware.
4
Virginia Mason Medical Center, Seattle, Washington.
5
UF Health Cancer Center, Orlando, Florida.
6
Immunomedics, Inc., Morris Plains, New Jersey.
7
Immunomedics, Inc., Morris Plains, New Jersey. dmg.gscancer@att.net.

Abstract

PURPOSE:

Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for delivery of SN-38, the active metabolite of irinotecan. This phase I trial evaluated this ADC as a potential therapeutic for pretreated patients with a variety of metastatic solid cancers.

EXPERIMENTAL DESIGN:

Sacituzumab govitecan was administered on days 1 and 8 of 21-day cycles, with cycles repeated until dose-limiting toxicity or progression. Dose escalation followed a standard 3 + 3 scheme with 4 planned dose levels and dose delay or reduction allowed.

RESULTS:

Twenty-five patients (52-60 years old, 3 median prior chemotherapy regimens) were treated at dose levels of 8 (n = 7), 10 (n = 6), 12 (n = 9), and 18 (n = 3) mg/kg. Neutropenia was dose limiting, with 12 mg/kg the maximum tolerated dose for cycle 1, but too toxic with repeated cycles. Lower doses were acceptable for extended treatment with no treatment-related grade 4 toxicities and grade 3 toxicities limited to fatigue (n = 3), neutropenia (n = 2), diarrhea (n = 1), and leukopenia (n = 1). Using CT-based RECIST 1.1, two patients achieved partial responses (triple-negative breast cancer, colon cancer) and 16 others had stable disease as best response. Twelve patients maintained disease control with continued treatment for 16 to 36 weeks; 6 survived 15 to 20+ months. No preselection of patients based on tumor Trop-2 expression was done.

CONCLUSIONS:

Sacituzumab govitecan had acceptable toxicity and encouraging therapeutic activity in patients with difficult-to-treat cancers. The 8 and 10 mg/kg doses were selected for phase II studies.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01631552.

PMID:
25944802
PMCID:
PMC4558321
DOI:
10.1158/1078-0432.CCR-14-3321
[Indexed for MEDLINE]
Free PMC Article

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