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Roche Up, J&J Down as Cancer Drug Combos Yield More Mixed Results

Xconomy San Francisco — 

Clinical testing of drug combinations that utilize cancer immunotherapies rolled on this weekend with mixed results. One Phase 3 study from Roche/Genentech in lung cancer succeeded, while another from Genmab and partner Johnson & Johnson spelled trouble for another possible drug combination.

Roche’s South San Francisco, CA, Genentech unit said its IMpower130 study, which combines immunotherapy atezolizumab (Tecentriq) with two chemotherapies (carboplatin and nab-paclitaxel (Abraxane)) succeeded. Without disclosing details, Genentech said the combination helped extend the lives of newly diagnosed advanced non-small-cell lung cancer patients, and helped reduce the risk of disease worsening or death.

Genentech said the side effects seen in patients taking the combination were “consistent with the known safety profiles” of each drug in the regimen.

The study is one of several lung cancer trials from Roche that combines its immunotherapy with either chemotherapy or other medicines. Three large drugmakers—Roche, Bristol-Myers Squibb, and Merck—each have a number of combination trials underway trying to capture control of the market and in the process, broaden the reach of immunotherapy. Lung cancer remains the leading cause of cancer death, and though in recent years immunotherapy has begun to make its mark, not everyone responds to treatment. Each company is trying to come up with the best possible combination to boost response rates without causing safety problems.

Multiple trials have now shown that adding chemotherapy to immunotherapy can help in lung cancer, so the IMpower130 result isn’t a surprise. Merck’s pembrolizumab (Keytruda)-chemo combination, for example, cut the risk of death or worsening disease in half compared to chemo alone in advanced NSCLC patients. It’s already FDA-approved. Merck just reported last week that a pembro-chemo combination was also successful in patients with the more aggressive, “squamous” form of NSCLC. And in a previous study, a Roche regimen that included chemotherapy, its immunotherapy atezolizumab (Tecentriq), and bevacizumab (Avastin), was better than the same regimen without immunotherapy. The IMpower130 results add another combination to the mix, though the details will be closely scrutinized when they’re made public at a future medical meeting. (Sorting through these and the other emerging combinations is going to be tough work for lung cancer specialists, as Xconomy reported here.)

Separately, Genmab reported that J&J will stop testing two studies combining its immunotherapy daratumumab (Darzalex) with immunotherapies known as checkpoint inhibitors. These drugs, among them pembrolizumab and atezolizumab, have been approved for a variety of cancers, but still only work on some 20 percent of patients. Combinations are seen as the key to expanding the reach of these drugs, and they’ve led to a slew of deals and alliances. More than 1,000 trials are underway to find the right mix of drugs—including 21 Phase 3 trials of immunotherapies producing data in 2018. (As Xconomy reported, cancer experts last year were skeptical of the scientific rationale behind many of studies, and concerned about unintended safety problems.)

So far, the results have been mixed. While lung cancer has seen several successful combination trials this year, for instance, other regimens haven’t been as encouraging. After a drug combination involving pembrolizumab and a drug known as an IDO inhibitor failed a Phase 3 study in skin cancer, several companies dialed back their IDO trials. Earlier this month, a combo of atezolizumab and the Exelixis (NASDAQ: EXEL) drug cobimetinib (Cotellic) failed a Phase 3 study in colorectal cancer.

Genmab and J&J have now produced a negative result too. The two companies had been hoping that combining daratumumab (Darzalex)—an FDA-approved multiple myeloma drug—with a checkpoint inhibitor might boost response rates in several cancers, and set up multiple trials. But an independent data monitoring board found a combination of daratumumab and atezolizumab produced no benefit and, worse, led to a “numerical increase in mortality-related events.” As a result, J&J will stop that study and a separate trial of daratumumab and its own checkpoint inhibitor (JNJ-67323283) in multiple myeloma. J&J could either change the doses in other daratumumab/checkpoint inhibitor trials or stop enrolling patients altogether, the companies said in a statement.