SSB Summary of Asco data:
Amgen (AMGN)/Abgenix's (ABGX) ABX-EGF: Another EGF-R inhibitor of interest
is the fully human monoclonal antibody called ABX-EGF being developed by
Amgen and Abgenix. Full details from a Phase II study of Amgen/Abgenix's
ABX-EGF as a monotherapy in refractory colorectal cancer patients were
presented at this meeting. The results reaffirmed previously response rate of
approximately 10% in patients, representing primarily partial responses.
Specifically, 10.1% (15/148) achieved a partial response with a median
duration of response of 5.2 months and median overall survival of 7.9 months.
38% (56/148) achieved stable disease. Response rates were generally similar
whether a patient failed two prior chemotherapies (ORR=11% or 9/80) or three
prior chemotherapies including Eloxatin (ORR=9% or 6/68) and despite the
level of EGFR expression. These results are similar to those demonstrated
with Erbitux. As expected, skin rash was the most frequent adverse event
with a potential correlation between response and rash. Pivotal Phase III
studies in refractory colorectal cancer patients are ongoing. Updated
interim data from an open-label Phase II study of ABX-EGF with paclitaxel and
carboplatin in lung cancer highlighted the preliminary promise of ABX-EGF in
this indication with approximately 26% (5/19) achieving a response rate (1
CR, 4 PR) at varying doses. Enrollment in the second part of this trial, of
175 patients, has been completed, which will compare ABX-EGF at 2.5
mg/kg/week dose with paclitaxel and carboplatin to those two agents without
the antibody.
Amgen/Abgenix---Key ABX-EGF Data Presented
ABX-EGF (panitumumab) is a fully human monoclonal antibody that binds to the
epidermal growth factor receptor (EGFR) as compared to ImClone/Bristol Myers-
Squibb's Erbitux, a chimeric monoclonal antibody. Amgen obtained rights to
this compound from Abgenix due to the Immunex acquisition. ABX-EGF is
currently in Phase II clinical trials for renal cell carcinoma, non-small
cell lung cancer (NSCLC), and colorectal cancer. Full details from a Phase
II study of Amgen/Abgenix's ABX-EGF as a monotherapy in refractory colorectal
cancer patients were presented at this meeting.
As a reminder, interim results were presented on the first 44 patients (40
evaluable) at the 2003 ASCO meeting, which demonstrated a 9-10% response
rate, a similar response rate that has been demonstrated with commercially-
available Bristol-Myers Squibb's Erbitux, a chimeric monoclonal antibody.
Last year, this study was expanded to enroll a total of approximately 150
patients, including patients failing an Eloxatin-based chemotherapy regimen
called FOLFOX, which has been become more broadly utilized. In late January,
Abgenix announced that a pivotal Phase III trial of ABX-EGF as a monotherapy
in advanced colorectal cancer patients had been initiated by partner, Amgen.
A second pivotal study has also been initiated in Europe. In our opinion,
the initiation of these pivotal studies imply that the results from the Phase
II study were sufficiently positive to proceed with these studies. Amgen and
Abgenix indicated that the study design was reviewed and approved by the FDA
under a Special Protocol Assessment (SPA) with the plan to submit an
application under accelerated approval guidelines. As a reminder, an SPA
provides clear regulatory guidelines of approval if a study as followed under
its submitted design achieves the targeted endpoints. We believe the study
is designed to be conducted in patients who have become refractory to
oxaliplatin (Sanofi Synthelabo's Eloxatin) as a third line therapy. Earlier
this year, Eloxatin was approved as a first line treatment for metastatic
colorectal cancer in combination with Fluorouracil (5-FU) and Leucovorin
(LV). While the exact details of the pivotal study for ABX-EGF have not been
provided, we believe that the trial is targeted to enroll a couple of hundred
patients with potential endpoints of response rate, duration of response and
tumor progression. Other endpoints may include survival. We estimate that
the study is likely to complete enrollment this year with a potential for
submission next year leading to a possible approval in late 2005 or early
2006.
Abstract #3511: ABX-EGF monotherapy in patients (pts) with metastatic
colorectal cancer (mCRC): An updated analysis. J. Randolph Hecht, et al
Study Design: This trial was designed to assess the safety and efficacy of
ABX-EGF as monotherapy in patients with metastatic colorectal cancer who have
previously failed various chemotherapy treatments. This multi-center open-
label Phase II study was initially targeted to enroll up to 100 patients and
was expanded to 150 patients last year to incorporate more patients that had
prior oxaliplatin (Eloxatin) therapy as well as patients with EGFR
overexpression of 1+ versus the prior criteria of 2+ or 3+ overexpression.
Patients received intravenous infusions of 2.5 mg/kg of ABX-EGF weekly over
an 8-week treatment cycle, for up to 6 cycles. All patients had failed prior
therapy with 54% having 2 prior agents while 46% of the patients had 3 prior
agents. Most patients had prior treatment with irinotecan while 72 patients
(49%) had prior oxaliplatin therapy.
Study Results: The results reaffirmed previously response rate of
approximately 10% in patients, representing primarily partial responses.
Specifically, 10.1% (15/148) achieved a partial response with a median
duration of response of 5.2 months and median overall survival of 7.9 months.
38% (56/148) of patients achieved stable disease. Response rates were
generally similar whether a patient failed two prior chemotherapies (ORR=11%
or 9/80) or three prior chemotherapies including Eloxatin (ORR=9% or 6/68)
and despite the level of EGFR expression. These results are similar to those
demonstrated with Erbitux. As expected, skin rash was the most frequent
adverse event with a potential correlation between response and rash.
Pivotal Phase III studies in refractory colorectal cancer patients are
ongoing. The response rates are summarized in table form below from the two
dosing cohorts as the study was expanded to enroll Eloxatin-experienced
patients. In term of safety, the drug was well tolerated, with mild to
moderate skin rash and fatigue was the most documented side effects. No
human anti-human antibodies (HAHA) have been documented in the patients
tested so far and importantly only one infusion related reaction had been
observed, which did not result in discontinuation of the drug.
Cohort A (n=104) Cohort B (n=44) Total (n=148)
Partial response at 10% (10 patients) 7% (3 patients) 9% (13 patients)
week 8
Overall response 11% (11 patients) 9% (4 patients) 10% (15 patients)
Stable disease 39% (41 patients) 34% (15 patients) 38% (56 patients)
Median duration of 6.4 months 4.2 months 5.2 months
response
Source: 2004 ASCO Meeting, Presentation, Hecht et al.
Abstract #7083: ABX-EGF in combination with paclitaxel and carboplatin for
advanced non-small cell lung cancer (NSCLC). Jeffrey Crawford, et al
Study Design: This study was an open-label dose escalation trial designed to
evaluate the safety, pharmacokinetics and efficacy of weekly dosing with ABX-
EGF given in combination with paclitaxel and carboplatin. A total of 19
patients with NSCLC were enrolled with doses of ABX-EGF at 1.0 mg/kg, 2.0
mg/kg and 2.5 mg/kg administered for up to eight six-week cycles.
Study Results: Data show that all doses of ABX-EGF were well tolerated when
given with paclitaxel and carboplatin in patients with NSCLC. In terms of
efficacy, updated interim data from an open-label Phase II study of ABX-EGF
with paclitaxel and carboplatin in lung cancer highlighted the preliminary
promise of ABX-EGF in this indication with approximately 26% (5/19) achieving
a response rate (1 CR, 4 PR) at varying doses. Enrollment in the second part
of this trial of 175 patients, has been completed which will compare ABX-EGF
at 2.5 mg/kg/week dose with paclitaxel and carboplatin to those two agents
without the antibody. |
