Date: 2016-04-18
Type of information: Interim results
phase: 2
Announcement: interim results
Company: Immunomedics (USA - NJ)
Product: labetuzumab govitecan (IMMU-130)
Action
mechanism: antibody drug conjugate/ADC. Labetuzumab Govitecan (IMMU-130) is an antibody drug conjugate involving an anti-CEACAM5 antibody, labetuzumab, conjugated to SN-38. SN-38 is the active metabolite of irinotecan(Camptosar®), which is used to treat certain solid cancers, particularly metastatic colorectal cancers, as a part of combination therapies, so its pharmacology and properties are well-known. It is currently being studied in patients with metastatic colorectal cancer (mCRC) who have received at least one prior irinotecan-containing regimen and had an elevated blood titer of carcinoembryonic antigen (CEA). Several dosing schedules were evaluated in three Phase I studies. Labetuzumab govitecan showed therapeutic activity in all three trials, but a more frequent dosing schedule, with administrations of the ADC once or twice-weekly for two weeks followed by a week off, appeared to be more active in patients with mCRC than when administered every other week.
Disease: metastatic colorectal cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: In the current Phase 2 study, patients with metastatic colorectal cancer are being treated in three-week cycles, receiving IMMU-130 either once weekly or twice-weekly for the first two weeks followed by one week of rest. Please refer to the Company Presentation for updated results from this multicenter study.
Latest
news: * On April 18, 2016, Immunomedics announced that labetuzumab govitecan continues to produce encouraging survival results in a multicenter, open-label Phase 2 study in patients previously treated with at least one irinotecan-containing regimen for their metastatic colorectal cancer (mCRC). Interim median progression-free survival (PFS) and overall survival (OS) for patients who received once-a-week of labetuzumab govitecan at the 8 or 10 mg/kg dose level are summarized below. For the 20 patients with prior treatment with regorafenib, bevacizumab, 5-fluorouracil, irinotecan and oxaliplatin-containing chemotherapies, the median PFS and OS were 3.9 and 6.7 months, respectively. * On June 2, 2015, Immunomedics announced an interim analysis of a mid-stage clinical study showed that its first-in-class antibody-drug conjugate (ADC), labetuzumab govitecan, produced encouraging survival results in patients previously treated with at least one prior irinotecan-containing regimen for their metastatic colorectal cancer (mCRC). For the 33 patients who received the ADC at the 8 or 10 mg/kg dose levels, the interim median
This Phase 2 study evaluated four dosing schedules. A total of 82 patients were enrolled to receive, in the first 2 weeks of a 21-day cycle, labetuzumab govitecan at 8 or 10 mg/kg onceweekly or twice a week at 4 or 6 mg/kg. There was no significant difference in safety and efficacy between the two once-weekly dosing schedules. For patient’s convenience, the once-aweek dose of 10 mg/kg was chosen for future studies in mCRC patients, possibly against regorafenib and/or in patients relapsed or refractory to regorafenib.
Labetuzumab govitecan remains well tolerated by patients. Among 75 patients with adverse events reported at the AACR conference, grades 3 and 4 adverse events across all doses, with occurrence of 2% or more, included neutropenia at 15%, diarrhea at 7%, and febrile neutropenia at 3%. For the 15 patients who received the ADC at 10 mg/kg once weekly, the designated dose, 33% reported grade 3 or 4 neutropenia but no incidents of febrile neutropenia or diarrhea.
Remarkably, despite repeated dosing, no antibody against labetuzumab or its SN-38 conjugate was detected in 460 blood samples (including baseline) drawn from 84 patients.
progression-free survival (PFS), a measure of the length of time the patient is living without their disease getting worse from the beginning of their labetuzumab govitecan treatments, was 4.4 months, with 22% of these patients still benefiting from their cancer not progressing.
“Compared to what has been reported in the medical literature, this result is very encouraging for patients with mCRC,” commented Dr. Efrat Dotan of Fox Chase Cancer Center, Philadelphia, PA, who presented the multicenter study at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) as one of the Principal Investigators. In terms of treatment response, in 32 patients with at least one evaluation following treatment with labetuzumab govitecan at the 8 or 10 mg/kg level, 1 patient had a partial response and 24 patients reported stable disease as their best response, to give a combined disease control rate of 78%. Treatment response was evaluated in accordance with the rules set by the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) using computed tomography as the imaging tool for tumor size measurements.
Labetuzumab govitecan was well tolerated by patients. At the optimal once-a-week doses of 8 and 10 mg/kg, grades 3 and 4 adverse events with occurrence of 5% or more included neutropenia (5% for both dose levels), and mild diarrhea (5% in the 8 mg/kg group only). Despite repeated dosing, no antibody against labetuzumab or its SN-38 conjugate was detected in blood samples from 74 patients over a 16-month period. At the time of analysis, 87 patients have been enrolled to receive the ADC in the first 2 weeks of a 21-day cycle. In addition to the 8 and 10 mg/kg once-weekly dose, other dosing levels and schedule evaluated included 4, 6, 9, and 12 mg/kg, each at a frequency of twice a week.
