Colon cancer; rectal cancer

August 28, 2017

Immunomedics reported that labetuzumab govitecan (IMMU-130) produced encouraging survival results in a multicenter, open-label phase II study in heavily-pretreated patients with metastatic colorectal cancer (mCRC). A total of 86 patients with progressive disease who had received prior therapy with an irinotecan-containing regimen, half of whom had completed five prior lines of therapy, were enrolled to receive labetuzumab govitecan either once-weekly at 8 and 10mg/kg, or twice-weekly at 4 and 6mg/kg, on weeks one and two of three-week repeated cycles. The two once-a-week dose schedules, showing comparable toxicity and efficacy, were chosen for further study. Median progression-free survival (PFS) for the 8mg/kg once-weekly dose and the 10mg/kg once-weekly dose was 4.6 (3.9 – 6.1) and 3.6 (2.1 – 6.0) months, respectively. Median OS (months) was 7.5 (5.7 – 16.1) and 6.4 (5.0 – 11.2). Labetuzumab govitecan was well-tolerated, with a manageable toxicity profile. Major toxicities (Grade >3) among all cohorts were neutropenia (16%), leukopenia (11%), anemia (9%) and diarrhea (7%). Anti-drug or anti-antibody antibodies were not detected.

February 2, 2015

PharmaEngine released results of a phase II study of PEP02 (MM-398, liposome irinotecan injection) in unresectable metastatic colorectal cancer (mCRC). The PEPCOL study evaluated the efficacy and safety of PEP02 (MM-398) in combination with 5-FU/LV (FUPEP regimen) or irinotecan plus 5-FU/LV (FOLFIRI regimens: FOLFIRI-1 or modified FOLFIRI-3) as a secondline therapy in patients with mCRC. The primary endpoint was the objective response rate (ORR). Fifty-five patients were randomized (FUPEP, n=28; FOLFIRI, n=27) and non-comparative randomly assigned to FUPEP (PEP02 80mg/m² d1, folinic acid (FA) 400mg/m² d1, 5-FU 2,400mg/m² d1-2) or FOLFIRI (FOLFIRI-1: irinotecan 180mg/ m² d1, FA 400mg/m² d1, 5-FU bolus 400mg/m² d1, 5-FU infusion 2,400mg/m² d1-2; or modified FOLFIRI-3: irinotecan 90mg/m² d1 and 3, FA 400mg/m² d1, 5-FU infusion 2,400mg/m² d1-2). Bevacizumab q2w (5mg/kg) was allowed in both arms as of June 2012. In the intent to treat population, the ORR of the FUPEP regimen was 14% (4/28), which compared favorably with FOLFIRI-1 (0%, 0/10) and was comparable to the modified FOLFIRI-3 regimen (18%, 3/17). Most common grade 3-4 adverse events reported in the respective FUPEP and the FOLFIRI arms were neutropenia (11% v. 30%) and diarrhea (21% v. 33%), which were numerically lower in the FUPEP arm than in the FOLFIRI arm; other aspects of the safety profiles were similar between the two arms. Based on the acceptable safety profile of the FUPEP regimen in this PEPCOL study, it was added as the third arm to the phase III metastatic pancreatic cancer (NAPOLI-1) study in which this FUPEP regimen (MM-398 + 5-FU/LV arm) met the primary endpoint of a statistically significant improvement in overall survival.

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