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By Ingfei Chen

Immune-Boosting Ipi

A new antibody approach holds promise for patients with melanoma and other cancers

By Ingfei Chen


This summer brought heady optimism that a drug with a tongue-twister name—ipilimumab, or ipi for short—could soon become the first novel therapy approved for advanced melanoma, the most dangerous type of skin cancer, in a dozen years. Research published in the Aug. 19 New England Journal of Medicine showed that ipi extended life in metastatic melanoma patients in rigorous phase III clinical trial testing, a feat achieved by no other treatment. A day earlier, pharmaceutical maker Bristol-Myers Squibb announced that the U.S. Food and Drug Administration (FDA) had granted the drug a priority review.

Until a decision comes back from the FDA, patients can explore compassionate-use access to ipilimumab at clinicaltrials.gov. But the drug isn’t a cure. Although a fortunate few patients have reaped an extraordinary payoff, it extends survival by a modest 3.6 months on average.

Malignant melanoma is visible as black spots that are invading lung tissue.Still, the enthusiasm over ipi was understandable, because once melanoma spreads to the lungs, brain or other locations, patients typically die within a year; about 8,700 Americans die annually from melanoma. The two drugs approved for the disease by the FDA—dacarbazine (DTIC-Dome) and interleukin-2 (Proleukin)—offer limited benefits.

But the recent, international ipi trial offers landmark proof that the medication’s new approach to cancer immunotherapy can work. “This drug psychologically has broken a major hurdle,” says study co-leader and oncologist Steven O’Day of the Angeles Clinic and Research Institute in Los Angeles. Ipi is a naturally occurring antibody that helps white blood cells attack the cancer—a job ipi performs by disengaging a receptor, called CTLA4, that’s found on the outside of these disease-fighting immune cells. Without ipi’s help, the receptor normally turns the immune cells off.

The new study tracked 676 individuals with stage III or IV melanoma whose cancer didn’t respond to other treatments. Some patients received intravenous infusions of ipi. Others took the antibody plus an experimental vaccine, or took the vaccine only. Bristol-Myers Squibb and Medarex, which jointly developed ipi, sponsored the trial.

Roughly one in 10 patients taking ipi alone saw substantial tumor shrinkage. Ipi recipients lived a median of 10 months, compared with 6.4 months in those taking only the vaccine, which offered little benefit. The antibody nearly doubled survival rates, with 23.5 percent of the ipi-only group alive at two years out. Some of these individuals are still going strong at four and a half years, O’Day says.

National Cancer Institute (NCI) medical oncologist Tito Fojo cautions, however, that the drug may cause serious side effects—like diarrhea and skin rashes from a hyperactive immune response—and if ipi is approved, it could be quite expensive. Other new targeted therapies cost thousands of dollars per month.

Researchers hope to improve upon the new immunotherapy to make it more powerful; similar antibodies are in development. O’Day and colleagues are exploring ways to bolster ipi’s benefits by adding chemotherapy or agents such as Avastin.

And a big question is whether ipi’s immune-boosting mechanism fights other malignancies. Phase II trials are testing it against prostate and lung cancer. “It looks promising,” says O’Day.

 

(image: © Dr. Cecil H. Fox / Photo Researchers Inc.)