Latest Immunotherapy Setback: Bristol Drugs Stumble in Kidney Cancer

Xconomy New York — 

The recent stumbles for cancer immunotherapy—specifically, combinations of treatments meant to help boost its effectiveness—continued late Tuesday with some disappointing news from one of the leaders in the field, Bristol-Myers Squibb.

Bristol (NYSE: BMY) said that a Phase 3 trial testing two of its immunotherapies together in newly diagnosed kidney cancer patients, a study called Checkmate-214, met one study goal and missed another. Enough people responded to treatment with Bristol’s nivolumab (Opdivo) and ipilimumab (Yervoy), compared to a course of mainstay kidney cancer drug sunitinib (Sutent), to declare success. But there wasn’t enough of a difference seen in the drug combination’s ability to keep cancer from spreading, compared to sunitinib.

Specifically, 41.6 percent of patients responded to nivolumab/ipilimumab treatment, compared to 26.5 percent of those on sunitinib. Patients on the Bristol drug combo saw their cancers held in check—what’s known as progression free survival—for a median of 11.56 months, compared to 8.38 months for sunitinib, but the results weren’t statistically significant.

It should be noted that there is a third study goal in Checkmate-214 tracking whether the nivolumab/ipilimumab combination ultimately helps patients live longer. Bristol is continuing it until can accrue that data, and success on that measure could help boost Bristol’s case for FDA approval. For its part, Bristol said it plans to share the results with regulators and pointed to the “totality of the Checkmate-214 data” in a statement, noting how long-lasting the patients’ responses to combo therapy were—the median duration of response measure hasn’t been reached yet, while the median response was 18.17 months for sunitinib.

“This is an important study in first-line renal cancer as these patients need new options,” said Vicki Goodman, Bristol’s development lead for melanoma and genitourinary cancers, in a prepared statement.

In the meantime, however, the study is the latest setback in the life sciences industry’s ongoing quest to use cancer immunotherapies in drug combinations to broaden their use. Immunotherapy drugs are now approved for several cancers, and in some cases produce stunning, long-lasting results for patients who might otherwise be at death’s door. But the majority of patients don’t respond to treatment, and researchers still don’t understand why. Drug companies are testing a slew of combinations hoping for better results, and while encouraging signs are being seen in some trials, there have been some notable failures in others.

Earlier this year, for example, safety problems caused the FDA to halt a Merck study testing its immunotherapy drug, pembrolizumab (Keytruda), together with two established therapies, pomalidamide (Pomalyst) and dexamethasone, in patients with multiple myeloma. And last month, a closely watched Phase 3 study from AstraZeneca testing two immunotherapies in tandem on newly diagnosed lung cancer patients missed its mark as well.

Some cancer experts polled by Xconomy in June feared that exuberance for immunotherapy might wane as failures in combination trials piled up. That hasn’t happened yet. The immunotherapy field is broad, full of multiple approaches simultaneously marching forward. One new form of cellular immunotherapy, called CAR-T, for instance, looks to be headed towards FDA approval for patients with certain types of blood cancers.

In investors’ eyes, meanwhile, AstraZeneca’s failure was particularly pertinent to Bristol. AstraZeneca’s study, called Mystic and still ongoing, is testing a similar type of immunotherapy tandem to ipilimumab/pembrolizumab. A combination of “checkpoint inhibitors” that help the immune system detect cancer, ipilimumab and pembrolizumab became the first cancer immunotherapy combination to win FDA approval, for melanoma.

Questions remain about the combination’s effectiveness compared to the added side effects and high cost, but its success and role in cancer care is critical to Bristol’s future standing in immunotherapy.

Bristol is studying the regimen in other cancers as well, among them a critical lung cancer study called Checkmate-227 that is expected to produce results next year. While caveats apply comparing one trial to another, with each new data point, Wall Street analysts still attempt to predict the likelihood that Checkmate-227 will succeed. Evercore ISI analyst Umer Raffat, for example, views the results of Checkmate-214 as “confirming the drug [combination] is active” and doesn’t think it makes a negative case for the lung cancer study.

Nonetheless, investors sent Bristol shares down about 2 percent in pre-market trading Wednesday.