Safety concerns forced investigators at Memorial Sloan-Kettering Cancer Center to suspend patient recruitment for an early-stage study of a closely watched approach to reengineering the immune system to fight cancer. Several days ago MSK updated a site on clinicaltrials.gov to note that it was halting recruitment for a small study using T cells reengineered with chimeric antigen receptors (CARs) against CD19-positive B cells for aggressive non-Hodgkin lymphoma, triggering concerns about the potential fallout at Juno Therapeutics, the biotech formed to commercialize the effort. And Sunday evening representatives for MSK revealed at the meeting of the American Association for Cancer Research in San Diego that the deaths of two patients spurred investigators to rethink the trial protocol on recruitment, revamping the patient profile to account for the threat of comorbidities while adjusting the dose "based on the extent of disease at the time of treatment."Memorial Sloan-Kettering's Michel Sadelain
Heated rumors were flying on Twitter over the weekend after MSK's Michel Sadelain acknowledged the halt, citing an unexplained safety issue that popped up in discussions at AACR. In their presentation at AACR on Sunday afternoon, MSK officials noted that 10 of 22 patients in the study had died.
Six patients died of either disease relapse or progression, said MSK, while two patients died in remission from complications related to allogeneic bone marrow transplantation. An additional two patients died within two weeks of receiving a CAR-T cell infusion.
"The first of these two patients had a prior history of cardiac disease and the second patient died due to complications related to persistent seizure activity," noted MSK's presentation. "As a matter of routine review of adverse events on study, our center made a decision to pause enrollment and review these two patients in detail."
Juno tells FierceBiotech that the study will soon be back on track, and is just as promising as it ever was.
In a statement to FierceBiotech midday on Sunday, the biotech stated: "Juno Therapeutics' partner institution Memorial Sloan Kettering Cancer Research Center proactively amended their protocols in the CD19 trial, which led to a hold while those amendments are reviewed. They are working closely with the FDA and all indications are that the trial will be enrolling again shortly. The MSKCC trial has shown the best response rate ever reported for salvage therapy in poor risk adult ALL. The Hutch and Seattle Children's Research Institute trials are unaffected and continue to show great promise. Juno's plans and timelines at MSKCC, The Hutch, Seattle Children's and other partner institutions are not impacted in any way and Juno plans to announce a further expansion of its plans in the coming weeks."
The chief focus of the suspended trial, which launched a year ago, is the maximum tolerated dose and safety of the therapy, with a secondary focus on progression-free survival. According to the government website, last updated on Thursday, the plan was to wrap the study in the spring of 2015. It's one of more than a dozen early human clinical studies planned to hustle along one of the leading efforts to use CAR technology to revolutionize the fight against cancer. The technology was used to launch Juno Therapeutics, one of the best financed efforts in biotechnology, which announced a $145 million A round a few months ago.
Juno is at the forefront of a bold experiment in the cancer field. Building on years of research, the biotech uses gene therapy tech to construct CAR-T cells. T cells--the so-called killer cells the immune system uses to hunt down and eliminate dangerous threats to human health, with the notable exception of cancer cells--are extracted from patients and then reengineered using benign viral vectors to express CARs that zero in on specific antigens on the surface of cancer cells. By multiplying and then injecting a swarm of these CAR-T cells into a patient with cancer, the scientists behind this venture believe that they can create a lasting "memory" in the immune system that will keep T cells on guard against cancer, either holding the disease at bay or extinguishing it entirely.
In very small human studies in patients with acute lymphoblastic leukemia, the CAR-T approach has spurred lasting remissions.
It has also stirred a legendary showdown between two rival groups of scientists and backers which have each staked a claim on what they expect to be a blockbuster new approach to fighting cancer. In one camp is Juno, with the backing of high-profile scientific founders at the Fred Hutchinson Cancer Research Center, Memorial Sloan-Kettering and Seattle Children's Research Institute. Investors, including Amazon's ($AMZN) Jeff Bezos, have put up the cash to organize Juno and commercialize the effort. The other camp is directed by none other than Novartis ($NVS), which in-licensed the work done by Carl June at the University of Pennsylvania and is bankrolling an ambitious effort to push a new therapy through the clinic. Both sides are now engaged in a bitter legal squabble over the rights to the technology, which Juno's backers claim was improperly purloined by June.
- here's the link to the study on clinicaltrials.gov