The maker of a drug approved to treat the blood cancer multiple myeloma has stopped a clinical trial combining it with an immunotherapy agent in lung cancer and stopped another study in multiple myeloma. The decision came after a review committee found a lack of benefit and higher number of deaths among lung cancer patients receiving the combination.
Janssen – a division of Johnson & Johnson – terminated a Phase I/IIb study of Darzalex combined with Roche immunotherapy drug Tecentriq in non-small cell lung cancer. In response to the findings in the lung cancer study, it also discontinued a Phase I trial of Darzalex with an in-house immunotherapy drug, JNJ-63723283. The decision was made after the data monitoring committee found a lack of benefit and a numerical increase in deaths among patients receiving Darzalex and Tecentriq, according to a press release by Danish drug maker Genmab, which developed Darzalex in partnership with Janssen.
Furthermore, Janssen said it informed health authorities about the events and has contacted partnering companies conducting studies combining Darzalex with PD-1 and PD-L1 inhibitors to discuss ceasing enrollment and dosing while the data are investigated, according to the press release.
Darzalex, known generically as daratumumab, is a drug that targets a cell surface protein called CD38, while Tecentriq inhibits PD-L1, a “checkpoint” on the immune system that allows cancer cells to evade detection. JNJ-63723283 targets PD-1, which similarly acts as an immune system checkpoint. Darzalex was approved for multiple myeloma in 2015 and has since become a backbone treatment for the blood cancer. Tecentriq, whose generic name is atezolizumab, was initially approved in 2016 and is labeled for urothelial carcinoma and non-small cell lung cancer.
It’s not the first time that checkpoint inhibitor combinations in multiple myeloma have run into trouble. Last July, the Food and Drug Administration placed a hold on two studies combining Merck & Co.’s PD-1 inhibitor, Keytruda – generic name pembrolizumab – with Celgene drugs Revlimid and Pomalyst, when an excessive number of patients receiving the combinations died. Revlimid and Pomalyst, which carry the respective generic names lenalidomide and pomalidomide, are combined with the steroid dexamethasone and, like Darzalex, are mainstays of multiple myeloma therapy, belonging to a drug class known as immunomodulators.
As a safety precaution in response to the hold placed on the Keytruda studies, the FDA also placed a partial hold on a study that combined a competing drug – Bristol-Myers Squibb’s Opdivo (nivolumab) – with Darzalex, Pomalyst and dexamethasone. Another study, combining BMS’ SLAMF7-targeting myeloma drug Empliciti (elotuzumab) with Pomalyst and Opdivo – was also placed on hold. However, BMS said in a Dec. 5 press release that the FDA had lifted the partial hold on those studies while maintaining a hold on a third one, which combines Opdivo, Empliciti and Pomalyst. A partial hold means that the study cannot enroll new patients, but participants experiencing benefit may continue to receive treatment.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Photo: NIH Image Gallery, Flickr
