Kite Presents Yescarta’s Encouraging Long Term ZUMA-1 Trial Results at ASH2020

On December 5th, Kite Pharma, a Gilead Company, announced their 4-year follow-up data from the monumental clinical trial ZUMA-1, which tested the efficacy and safety of their CAR-T cell therapy, Yescarta (axicabtagene ciloleucel) in adult patients with refractory large B-cell lymphoma.

Large B cell lymphoma is the most common subtype of Non-Hodgkin lymphoma responsible for affecting older adults. Refractory large B-cell lymphoma remains a major cause of mortality. Managing this disease remains a challenge with limited treatment options such as high-dose chemotherapy followed by stem cell transplantation. However, with the advancement of immunotherapy, personalized treatments like chimeric antigen T (CAR-T cell therapy) have come to the forefront.

Yescarta – CAR-T Therapy

CAR-T therapy takes advantage of the host immune cell to mount a response against tumors. To date, this kind of therapy has been useful against hematological tumors. In this therapy, the T-cells are collected from the patients, genetically modified to target certain surface proteins, propagated in vivo, and then infused back into the patients. Yescarta is a CAR-T cell therapy approved by the FDA in 2017, which uses cluster differentiation 19 (CD 19) as a stimulatory molecule and CD-28 as a costimulatory molecule.

ZUMA-1

The FDA approval of Yescarta was based on the ZUMA-1 trial, a multicenter, randomized blinded, Phase 3 clinical trial which enrolled 111 patients, of which 101 received the CAR-T cell infusion. The study met its primary endpoint with an 87% overall response rate. Previously, 3-year follow-up data showed an overall survival of 50%. The 4-year follow-up data presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition showed an overall survival of 44%. This is astounding, given that the T-cell infusion was a one-time therapy. Further, of the 21 patients who provided blood samples, 67% still had CAR-T cell markers while 91% had normal B-cells. This showed that CAR-T cell persistence is not necessary for durable remissions.

“With these first-ever four-year data from a pivotal CAR T clinical trial in lymphoma, we continue to show the potential long-term survival of Yescarta in relapsed/refractory large B-cell lymphoma and push the boundaries of what is possible with this CAR T treatment,” said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. “And equally importantly, we are encouraged by similar trends in long-term survival with real-world experience, with thousands of patients treated since Yescarta first became available.”

“With close to half of patients still alive after a single infusion of axicabtagene ciloleucel, we are transforming the way relapsed or refractory large B-cell lymphoma can be treated,” Dr. Frederick said L. Locke, Co-Lead Investigator at Moffitt Cancer Center in Florida. “As a practicing oncologist, I continue to see these patients in the clinic, and this overall survival data confirms the durability of CAR T-cell therapy in a patient population that previously exhausted all viable treatment options.”

Competition

The major competition for Yescarta is Novartis’ Kymriah, which is also a CD-19 targeting CAR-T cell therapy. Both drugs initially had a rough start, with Kymriah running into production issues in 2018 and Yescarta suffering reimbursement issues with insurance companies. Besides, both these therapies come with a huge price tag of around $400,000. With both these drugs starting slow, it will be interesting to see if the long-term safety data will tilt the market towards Yescarta.

It is to be noted here, BMS’s CAR-T cell therapy, liso-cel, is also currently under FDA review. The drug was supposed to be discussed in mid-august, but due to COVID-19, the FDA postponed the verdict. The company has been running against a deadline from the investors to get the drug approved by the end of the year. With FDA visiting sites in early December, Novartis and Kite Pharma may soon have BMS joining the race.

By T. Chakraborty, Ph.D.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: ASH2020: Incyte Presents Positive Phase 3 Data for cGVHD Drug, Ruxolitinib

References

1. https://www.kitepharma.com/news/press-releases/2020/12/yescarta-is-first-car-t-cell-therapy-to-demonstrate-high-response-rates-and-durable-clinical-benefit-in-a-pivotal-indolent-non-hodgkin-lymphoma-study
2. https://ash.confex.com/ash/2020/webprogram/Paper134362.html
3. https://news.bms.com/news/details/2020/Bristol-Myers-Squibb-Provides-Regulatory-Update-on-Lisocabtagene-Maraleucel-liso-cel/default.aspx

Author

Tulip Chakraborty