Another prospective combination of cancer immunotherapy drugs has shown its warts in clinical testing. The latest example: an experimental treatment from Five Prime Therapeutics fell short of expectations when combined with one of the leading immunotherapy drugs, nivolumab (Opdivo), from Bristol-Myers Squibb, in a small study.
In a Phase 1 clinical trial of pancreatic cancer patients, 43 percent, or 88 of the 205 people tested experienced a serious side effect after receiving Five Prime’s (NASDAQ: FPRX) cabiralizumab and Bristol’s nivolumab, and 13 percent of them dropped out of the study. Meanwhile just 10 percent of patients responded to treatment. The data were contained in an abstract that South San Francisco, CA-based Five Prime will present on Saturday during the annual meeting of the Society for Immunotherapy of Cancer (SITC).
Drugmakers have been testing a slew of cancer drug combos in the hopes of expanding the reach of immunotherapy. But several combinations have fallen short of expectations, either due to lack of effectiveness or safety problems. Cabiralizumab/nivolumab looks like an “active combination,” according to a note from RBC Capital Markets analyst Kennen MacKay, but its results so far are below expectations. What’s more, the side effects observed in the Five Prime study are the latest sobering example of the problems that can crop up during these tests. The news was enough to spook investors, and Five Prime’s stock price sank 34 percent at mid-day on Tuesday to $28.62 per share.
Cabiralizumab is an antibody drug that blocks a protein, colony-stimulating factor-1 (CSF1), on the surface of macrophages. Nivolumab, meanwhile, is one of a handful of FDA-approved cancer immunotherapy drugs called checkpoint inhibitors, which have shown promise treating cancers of the skin, lung, and more. Two years ago, Bristol paid Five Prime $350 million up front in a partnership to co-develop cancer immunotherapies, including cabiralizumab. The data to be presented at SITC are the first clinical results for the cabiralizumab-nivolumab combination.
Leerink Partners analyst Michael Schmidt wrote that the serious side effects seen, such as high levels of an enzyme called creatinine phosphokinase, could raise questions among investors until the full set of data are presented at the SITC conference later this week.
Immunotherapies have produced promising results in a number of cancers, but they don’t work for everyone, which is one reason that companies are testing combinations of drugs in an effort to bring this approach to more patients. The first FDA-approved immunotherapy combination, for instance, the pairing of Bristol drugs ipilumab (Yervoy) and nivolumab, has shown that it can modestly improve survival in melanoma patients compared to nivolumab alone. But that combination has also shown an increase in side effects, including heart and liver trouble.
Other cancer immunotherapy combinations have struggled as well. AstraZeneca (NYSE: AZN) saw a closely watched combination of immunotherapy drugs fail a key test in newly diagnosed lung cancer patients. In June, patient deaths led Merck (NYSE: MRK) to stop a multiple myeloma study testing its immunotherapy pembrolizumab (Keytruda) in combination with two older treatments for the disease. The FDA later said that scientists monitoring the study found a higher rate of death in patients who received the drug combo, and it warned physicians against using the treatments together.
The SITC conference runs from Wednesday through Sunday. Five Prime has scheduled a conference call on Saturday to discuss the data from its study.
Pancreatic cancer cells, image from National Cancer Institute.