SGN-15/Docetaxel Is Well Tolerated in a Phase II Investigation

ORLANDO—SGN-15 (a monoclonal antibody conjugated to doxorubicin) plus docetaxel (Taxotere) was well tolerated in patients with metastatic breast cancer or colorectal cancer and showed objective responses, according to a phase II trial.

Lisle M. Nabell, MD, assistant professor of hematology/oncology, University of Alabama, Birmingham, presented the results at a poster session of the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 55).

The linking antibody of SGN-15 (chimeric BR96-doxorubicin, Seattle Genetics) is directed at the Lewis Y antigen. Both breast and colorectal tumors express the antigen. The agent is rapidly internalized. Hydrazone cleavage releases the doxorubicin intracellularly. A 200-mg dose of SGN-15 delivers 6 mg of doxorubicin directly to the tumor cells. "It’s biological targeting at its best, if it works," Dr. Nabell said.

Preclinical trials indicated a synergy when SGN-15 was combined with a taxane agent. A prior phase I study of the SGN-15/docetaxel combination encountered unacceptable gastrointestinal (GI) toxicities. But investigators at the University of Alabama decided to try a different dosing schedule during a phase I trial in which 16 patients received escalating doses of SGN-15 with a fixed dose of docetaxel.

The phase II study involved two cohorts of patients with metastatic breast cancer or metastatic colorectal cancer. The results from each cohort were analyzed separately. "The questions were, is the GI toxicity acceptable and is it effective," Dr. Nabell said.

Eligibility for the study included metastatic disease, Lewis Y antigen expression, and a life expectancy of greater than 3 months. Patients were allowed to have been previously treated with chemotherapy for their metastatic disease.

The 18 colorectal cancer patients ranged in age from 29 to 77 years (median, 58.5). Eleven were male. The 26 breast cancer patients evaluated to date ranged in age from 35 to 78 years (median, 53.5). One was male. Patients received weekly SGN-15 175 mg/m2 and docetaxel 30mg/m² for 6 weeks, followed by a 2-week rest period.

Two patients in the colorectal cohort and six in the breast cancer cohort experienced reversible grade 3 or greater nausea and vomiting. An asymptomatic grade 3 or greater increase in lipase levels was seen in three colorectal patients and two breast cancer patients.

Grade 3 or greater neutropenia occurred in one colorectal cancer patient and two breast cancer patients. There was no grade 3 or higher diarrhea, and only one case of grade 3 or higher mucositis (in a colorectal cancer patient).

Investigators saw an objective response in one colorectal cancer patient and in three breast cancer patients, including one patient with a 70% reduction in hepatic disease. Disease stabilization was seen in four colorectal cancer patients and 6 breast cancer patients. The breast cancer study continues to enroll patients.

"It’s a novel compound," Dr. Nabell said. "The idea that we could deliver a drug intracellularly is provocative. But we have to wait until the end of the phase II study to see if it warrants further evaluation in a phase III trial."