Study of Labetuzumab Govitecan in Participants With Metastatic Colorectal Cancer

• Labetuzumab Govitecan (LG) (Drug), also known as hMN14-SN38, Labetuzumab-SN38, Antibody-Drug Conjugate, IMMU-0130, GS-0130: Administered as a slow intravenous (IV) infusion.

Primary outcomes

• Percentage of Participants With Adverse Events and Serious Adverse Events (SAEs) [From first dose date up to approximately 2 years after the last dose or until disease progression]
• Percentage of Participants With Laboratory Abnormalities [From first dose date up to approximately 2 years after the last dose or until disease progression]

Secondary outcomes

• Duration of Response [From first documentation of PR or CR to the earlier of the first documentation of PD or death from any cause (Up to approximately 2 years after the last dose or until disease progression)]: Duration of response (DOR) is defined as the interval from the first documentation of PR or CR to the earlier of the first documentation of disease progression (PD) or death from any cause.
• Progression-free Survival [From first dose date up to 12 weeks post treatment (Up to approximately 2 years after the last dose or until disease progression)]: Progression free survival (PFS) is defined as the interval from the start of study drug treatment to the earlier of the first documentation of disease progression or death from any cause.
• Time to Progression [From first dose of study treatment up to PD (Up to approximately 2 years after the last dose or until disease progression)]: Time to progression is defined as the interval from the first dose of treatment to the first documentation of disease progression (PD).
• Overall Survival [From first dose date up to approximately 2 years]: Overall survival is defined as the time from start of study drug treatment to death from any cause.
• Time-to-treatment Failure [From first dose date up to 8 treatment cycles (each cycle = 21 days) (Up to approximately 24 weeks)]: Time to treatment failure (TTF) is defined as the interval from the start of treatment to the earlier of the first documentation of disease progression or death due to any cause, the permanent cessation of LG therapy due to all reasons except progressive disease, participant died or lost to follow up.
• Change from Baseline in Carcinoembryonic Antigen (CEA) Serum Levels [From first dose date up to approximately 2 years after the last dose or until disease progression]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Histologically or cytologically confirmed colorectal adenocarcinoma.
* Stage IV (metastatic) disease.
* Previously treated with at least one prior irinotecan-containing regimen for colorectal cancer.
* Adequate performance status (Eastern Cooperative Oncology Group (ECOG) 0 or 1).
* Expected survival > 6 months.
* Carcinoembryonic antigen (CEA) plasma levels > 5 ng/mL.
* Measurable disease by computed tomography (CT) or Magnetic resonance imaging (MRI).
* At least 4 weeks beyond treatment (chemotherapy, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities.
* At least 2 weeks beyond corticosteroids.
* 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 ≤ 1.5 x IULN, bilirubin ≤ institutional upper limit of normal (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 by National cancer institute common terminology criteria for adverse events (NCI CTC) v4.0.

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 or known central nervous system (CNS) metastatic disease.
* Individuals with CEA plasma levels > 1000 ng/mL must be approved in advance by the Sponsor.
* Presence of bulky disease (defined as any single mass > 10 cm in its greatest dimension).
* 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 human immunodeficiency virus (HIV) positive, hepatitis B positive, or hepatitis C positive.
* Known history of unstable angina, myocardial infarction, or congestive heart failure present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
* Known history of clinically significant active chronic obstructive pulmonary disease (COPD), or other moderate-to-severe chronic respiratory illness present within 6 months.
* Infection requiring intravenous antibiotic use within 1 week.
* 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.

• Govindan SV, Goldenberg DM. New antibody conjugates in cancer therapy. ScientificWorldJournal. 2010 Oct 12;10:2070-89. doi: 10.1100/tsw.2010.191. PMID 20953556
• Govindan SV, Cardillo TM, Moon SJ, Hansen HJ, Goldenberg DM. CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin Cancer Res. 2009 Oct 1;15(19):6052-61. doi: 10.1158/1078-0432.CCR-09-0586. Epub 2009 Sep 29. PMID 19789330
• Moon SJ, Govindan SV, Cardillo TM, D'Souza CA, Hansen HJ, Goldenberg DM. Antibody conjugates of 7-ethyl-10-hydroxycamptothecin (SN-38) for targeted cancer chemotherapy. J Med Chem. 2008 Nov 13;51(21):6916-26. doi: 10.1021/jm800719t. Epub 2008 Oct 22. PMID 18939816
• Govindan SV, Griffiths GL, Hansen HJ, Horak ID, Goldenberg DM. Cancer therapy with radiolabeled and drug/toxin-conjugated antibodies. Technol Cancer Res Treat. 2005 Aug;4(4):375-91. doi: 10.1177/153303460500400406. PMID 16029057
• Dotan E, Cohen SJ, Starodub AN, Lieu CH, Messersmith WA, Simpson PS, Guarino MJ, Marshall JL, Goldberg RM, Hecht JR, Wegener WA, Sharkey RM, Govindan SV, Goldenberg DM, Berlin JD. Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer. J Clin Oncol. 2017 Oct 10;35(29):3338-3346. doi: 10.1200/JCO.2017.73.9011. Epub 2017 Aug 17. PMID 28817371

• Gilead Study Director, Study director, Gilead Sciences