Labetuzumab Govitecan Active in Heavily Pretreated mCRC

Monotherapy with labetuzumab govitecan is active in heavily pretreated patients with metastatic colorectal cancer (mCRC) and has an acceptable safety profile, a study presented at the American Academy for Cancer Research (AACR) Annual Meeting 2016 has shown.¹

Because there continues to be an urgent need for better treatment strategies to improve outcomes of patients with mCRC, researchers developed labetuzumab govitecan, a conjugate of a humanized antibody to CEACAM5 that is linked site-specifically to the active metabolite of irinotecan SN-38.

For the phase 2 study, researchers enrolled 86 patients with mCRC with a carcinoembryonic antigen level greater than 5 ng/mL and who had received a median number of 5 prior therapies, including prior irinotecan-containing therapy. Participants received labetuzumab govitecan at doses ranging from 4 to 10 mg/kg once or twice weekly for 2 weeks of each 3-week cycle. Treatment was continued until disease progression or unacceptable toxicity.

Results showed that the most common treatment-related adverse events were nausea, fatigue, vomiting, and diarrhea. Grade 3 and 4 treatment-related adverse events included neutropenia (15%), anemia (6%), and diarrhea (2%). All patients who required toxicity-related dose reductions or interruptions recovered with major consequences.

In terms of efficacy, the weekly regimen appeared superior with respect to disease control rate, progression-free survival, and overall survival compared with the twice weekly regimen. Of the patients who received 10 mg/kg every week, 78% had stable disease vs 7% of those who received 6 mg/kg twice weekly.

Researchers found that median progression-free survival with labetuzumab govitecan 10 mg/kg once weekly was 4.6 months compared with 3.7 months for 6 mg/kg twice weekly. Median overall survival was 9.3 months and 7.4 months, respectively.

Based on these findings, researchers will assess labetuzumab govitecan at a dose of 10 mg/kg weekly for 2 weeks in 21-day cycles for future studies.

Reference

1. Dotan E, Cohen SJ, Starodub AN, et al. Labetuzumab govitecan (IMMU-130), an anti-CEACAM5/SN-38 antibody-drug conjugate, is active in patients (pts) with heavily pretreated metastatic colorectal cancer (mCRC): phase II results. Oral presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.