MIAMI BEACH-Heat shock protein peptide complex-96 (HSPPC-96, Oncophage), an individualized cancer vaccine, produced complete responses in two patients with metastatic melanoma and long-term stable disease in several others during an Italian phase I-II trial.
MIAMI BEACHHeat shock protein peptide complex-96 (HSPPC-96, Oncophage), an individualized cancer vaccine, produced complete responses in two patients with metastatic melanoma and long-term stable disease in several others during an Italian phase I-II trial.
Giorgio Parmiani, MD, of the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan, sent results on 39 patients (abstract 799) for presentation at Molecular Targets and Cancer Therapeutics, an international conference cosponsored by the American Association for Cancer Research (AACR), National Cancer Institute (NCI), and European Organization for Research and Treatment of Cancer (EORTC).
None of the patients had any toxic reactions to the vaccinenot even skin irritation, Dr. Parmiani told the press by telephone from Italy. He is the deputy scientific director and head of the immunotherapy unit at the Institute.
There were two complete responders among 28 patients who had measurable disease after surgery to excise their tumors (see Figure). They have been followed for 559+ and 703+ days, respectively. Three others have maintained stable disease for more than 5 months.
Among 11 patients who had no measurable disease after surgery, two have been disease-free for more than 1 year, Dr. Parmiani said.
"Overall survival appears to be unusual in this group of patients," he said, noting that median survival is usually about 6 months for patients with stage IV melanoma.
HSPPC-96 uses heat-shock proteins derived from the tumors of each individual patient to make a unique vaccine for each patient. "It is important that the protein comes from the patient’s own tumor because each tumor is different as far as this antigen is concerned," Dr. Parmiani said.
The vaccine was administered weekly for 4 weeks, followed by a 4-week interval, after which some patients received a second cycle of four vaccinations.
Significantly, the researchers reported that immune response appeared to correlate with clinical response and to be specific to melanoma. An assay done in 23 patients found that after vaccination, nearly half (47.8%) had an increase in T cells recognizing MART-1 and gp100, two antigens specific to melanoma. Expression of class I HLA and the melanoma antigens was high in 5 of 6 clinical responders, but in only 3 of 13 nonresponders.
"Several patients also developed an immune reaction against the tumor," Dr. Parmiani said. "Those that did not respond clinically had low immune response against the tumor."
Phase III Trials
Dr. Parmiani concluded that the results strongly support advancing the vaccine in randomized trials. Co-investigator Jonathan Lewis, MD, PhD, chief medical officer of Antigenics, Inc., the vaccine developer, said the company plans to start a phase III trial with several hundred patients in Europe and the United States by early 2002.
Antigenics is already conducting a phase III trial in patients with renal cancer, and the US Food and Drug Administration (FDA) has awarded the vaccine fast-track development status for that disease. Additional trials are underway in colorectal, gastric, and pancreatic cancers, Dr. Lewis said.