Presenter: L. Saltz Presenter's Affiliation: Memorial Sloan-Kettering Cancer Center Type of Session: Scientific
In a previous trial (reported at ASCO last year), IMC-C225, in combination with CPT-11, was demonstrated to have a 22.5% response rate in 120 patients with CRC refractory to CPT-11 treatment.
A tumor xenograft model of EGFR-expressing CRC demonstrated some benefit of C225 as monotherapy.
Based upon these results, a study was undertaken to assess activity of IMC-C225 as monotherapy in patients with CPT-11-refractory CRC.
Materials and Methods
Patients recruited had measurable disease, demonstrated disease progression on CPT-11, and had tumors which expressed EGFR.
Inclusion criteria required ECOG Performance Status 0-2.
Intercurrent chemotherapy post CPT-11 failure was an exclusion criterion.
Time from cancer diagnosis to initiation of the study was a mean of 13 months in these patients.
Median ECOG performance status was 0, though 20% had a performance status of 2.
EGFR immunohistochemical staining demonstrated 1+ staining in 30% of patients, 2+ in 53%, and 3+ in 17%.
140 patients were recruited; of these, 105 possessed tumors which expressed EGFR.
Of these, 57 were treated. 44 patients had colonic primary tumor and 13 had rectal tumors.
Treatment on day #1 included premedication with Benadryl, followed by a 20mg test dose of C225. Patients then received a 400 mg loading dose. They then 250 mg weekly.
Studied endpoints included analysis of toxicity/tolerability, as well as responsiveness of tumors to treatment.
The majority of patients (86%) had an acneiform reaction. Eighteen percent of patients experienced grade 3/4 toxicity. This rash was self-limited, typically appearing in week 3-4 of treatment. Treatment with antibiotics did not alter the duration of symptoms.
The other predominant side effect was allergic reaction, in 5% of patients.
Other side effects (nausea, vomiting, diarrhea, asthenia) occurred at levels likely attributable to the primary disease process, though no specific attempt was made to further qualify this.
6/57 (10.5%) have had a partial response (PR) and 21 (36.8%) have had stable disease (SD) on C225 monotherapy.
Median duration of response has not been reached.
Median time to progression (TTP) was 50 days.
Monotherapy with IMC-C225 is well tolerated in these patients.
It produced objective responses in patients with treatment-refractory CRC.
This is an exciting study which will require validation in a phase 3 trial.
Many in the oncology community are expecting this drug to make a big impact in the future of cancer care.
The drug appears to be well tolerated with very mild toxicity.
Future studies will evaluate the combination of C225 with chemotherapy and radiation therapy regimens for a variety of cancers.
Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.
Sep 16, 2011 - The epidermal growth factor receptor EGFR gene is involved in the development of KRAS-pancreatic cancer; and the vaccinia virus construct GLV-1h153 may be a promising oncolytic agent for the treatment and monitoring of pancreatic cancer, according to two experimental studies presented at the American Association for Cancer Research International Conference on Frontiers in Basic Cancer Research, held from Sept. 14 to 18 in San Francisco.