Reference Detail

Ref Type

Journal Article

PMID

(28817371)

Authors

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

Title

Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology	35	29	2017 Oct 10	3338-3346	J Clin Oncol

URL

Abstract Text

Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer. Patients and Methods Eligible patients with at least one prior irinotecan-containing therapy received labetuzumab govitecan once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles. End points were safety, response, pharmacokinetics, and immunogenicity. Results Eighty-six patients who had undergone a median of five prior therapies (range, one to 13) were each enrolled into one of the four cohorts. On the basis of Response Evaluation Criteria in Solid Tumors 1.1, 38% of these patients had a tumor as well as plasma carcinoembryonic antigen reduction from baseline after labetuzumab govitecan treatment; one patient achieved a partial response with a sustained response spanning > 2 years, whereas 42 patients had stable disease as the best overall response. Median progression-free survival and overall survival were 3.6 and 6.9 months, respectively. The major toxicities (grade ≥ 3) among all cohorts were neutropenia (16%), leukopenia (11%), anemia (9%), and diarrhea (7%). The antibody-drug conjugate's mean half-life was 16.5 hours for the four cohorts. Anti-drug/anti-antibody antibodies were not detected. The two once-weekly dose schedules, showing comparable toxicity and efficacy, were chosen for further study. Conclusion Monotherapy with labetuzumab govitecan demonstrated a manageable safety profile and therapeutic activity in heavily pretreated patients with metastatic colorectal cancer, all with prior irinotecan therapy. Further studies of labetuzumab govitecan treatment alone or in combination with other therapies in earlier settings are indicated.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Labetuzumab govitecan	Labetuzumab govitecan	0	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Labetuzumab govitecan		IMMU-130	CEACAM5 Antibody 7	Labetuzumab govitecan (IMMU-130) is an antibody-drug conjugate comprised of CEACAM5 monoclonal antibody linked to the active metabolite of irinotecan (SN-38), which has potential antitumor activity (Journal of Clinical Oncology 2015 33:3_suppl, 625-625, PMID: 28817371, PMID: 30822636).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References