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.
June 8, 2009
Keryx reported positive results from a phase II trial of perifosine for the treatment of colon cancer. This US, randomized, double-blind, placebo-controlled study enrolled 38 subjects with 2nd or 3rd line metastatic colon cancer. The subjects received capecitabine (Xeloda; standard of care) at a dose of 825 mg/m2 twice daily (total daily dose of 1650 mg/m2) on days 1-14 every 21 days, plus either perifosine or placebo at 50 mg daily. Treatment continued until disease progression. Of the 38 enrolled subjects, 35 were evaluable for response. The primary endpoints were time to progression (TTP), overall response rate (ORR) and the clinical benefit rate (CBR). The median time to progression was 28.9 weeks in the perifosine/capecitabine arm compared to 11 weeks in the capecitabine /placebo arm (p-value&equiv0.0006). In addition, perifosine/capecitabine more than doubled the ORR and almost doubled the Clinical Benefit Rate versus capecitabine/placebo. Treatment was well tolerated.
June 1, 2009
The Burzynski Research Institute reported positive results from a phase II trial of antineoplaston (ANP) therapy for the treatment of colon cancer. This study enrolled 65 subjects with metastatic colon cancer at the Kurume University School of Medicine, Japan. The subjects were randomized to receive intrahepatic infusion of 5-FU or intrahepatic infusion of 5-FU plus intravenous (IV) ANP therapy. ANP therapy consisted of a 50-100 g IV infusion of Antineoplaston A10 given daily for seven days following hepatic resection and 10 g of oral Antineoplaston AS2-1 given daily for one year. The primary endpoint was the difference in overall survival between the two groups. The five-year survival rate was significantly higher in the 5-FU plus ANP therapy arm, at 62% versus 32% in the 5FU-only arm. The mode of recurrence was also different in the two study arms. In the 5FU-only arm, recurrences affected multiple organs in 69% of the subjects, while in the 5-FU plus ANP therapy arm, recurrences affected multiple organs in only 34% of subjects. This provided for a higher complete second resection rate in the 5-FU plus ANP therapy arm (61% versus 35%).