NEW YORK-A monoclonal antibody with high affinity for an ovarian tumor-associated antigen has shown promising activity in preliminary results from a large phase III study, said Jonathan S. Berek, MD, chief of the Division of Gynecology
NEW YORKA monoclonal antibody with high affinity for an ovarian tumor-associated antigen has shown promising activity in preliminary results from a large phase III study, said Jonathan S. Berek, MD, chief of the Division of Gynecology and Oncology, UCLA School of Medicine.
The antibody, known as oregovomab (OvaRex, AltaRex Corp., Waltham, Massachusetts), was clinically active in multiple studies of stage III-IV ovarian cancer patient populations. "The clinical activity, even with second-line chemotherapy, suggests new strategies for combined modality treatment," Dr. Berek said at the Chemotherapy Foundation Symposium XIX (abstract 30).
Oregovomab, a murine monoclonal antibody, has a high affinity for cancer antigen 125 (CA 125). In clinical studies, bioactivity correlating with clinical benefit has been observed in more than half of treated patients.
The agent’s "benign safety profile" makes it practical for real-world application, Dr. Berek said. Data from six trials including more than 400 patients suggest a safety profile similar to placebo, with infrequent and easily managed allergic responses (ie, pruritus) to the foreign protein.
A series of studies to date (prospective randomized and nonrandomized) show that this monoclonal antibody induces cellular and humoral responses across a wide range of ovarian cancer patients, notably in those with available circulating CA 125 and those who mount a potent immune response to treatment, defined as prolonged time to disease relapse.
More precise information on the clinical utility of oregovomab will be forthcoming from a large, double-blind, placebo-controlled trial including 345 stage III-IV ovarian cancer patients enrolled at 52 centers in Canada and the United States.
Antibody or placebo is given 4 to 10 weeks after successful primary surgery and platinum-based chemotherapy (normalized CA 125 and no residual disease).
Dr. Berek presented an interim analysis from this trial including the first 252 enrolled patients with a median follow-up of almost 9 months. The analysis, conducted by an independent third party to protect the integrity of the blinding, suggests that the antigen-targeted antibody reduces risk of relapse by 20% vs placebo. There was a 59% improvement in time to relapse (7.3 vs 4.6 months), with 6-month relapse-free survival of 69% vs 45% for placebo.
Another interim finding was that high serum CA 125 levels after primary therapy predicted shorter time to relapse. In patients deemed high risk (baseline CA 125 greater than 15 U/mL), time to relapse was 6.9 months vs 18.7 months in lower-risk patients with lower baseline CA 125 levels.
Patients who mounted an immune response to therapy had a favorable clinical outcome, a finding expected based on previous observations and confirmed in a separate double-blind study correlating immune response to clinical benefit. "Such responses are seen in about 50% of patients," Dr. Berek said.
As of this 8.6-month interim analysis, about half of the patients have not relapsed (33% and 58% for high- and low-risk patients, respectively). Investigators expect that final data, which will include an additional 24 months of follow-up, will show 27% of patients have not relapsed (10% and 35% for high- and low-risk, respectively).
"It will be of interest to establish how an immunotherapy may augment the activity of chemotherapy as the data continue to emerge," Dr. Berek said.
Oregovomab might augment salvage chemotherapy benefit in clinical relapsers, a hypothesis that is under investigation in a nonrandomized trial of 20 patients. Concurrently, clinical trial groups including the European Organization for the Research and Treatment of Cancer (EORTC) are evaluating oregovomab in combined treatment studies.