On December 11, 2017 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company developing innovative cellular immunotherapies for the treatment of cancer, and Celgene Corporation (NASDAQ: CELG) reported additional data from the TRANSCEND study of JCAR017 (lisocabtagene maraleucel; liso-cel) in patients with relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (NHL) in a presentation at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Celgene, DEC 11, 2017, View Source [SID1234522552]).

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"We are highly encouraged by the latest efficacy and tolerability data, particularly at dose level two, as these are patients with a poor prognosis who need better treatment options," said Sunil Agarwal, M.D., Juno’s President of Research and Development. "These data support a potential best-in-class profile and further support the importance of a defined cell product. We continue to enroll our pivotal cohort in DLBCL patients and over the next twelve to eighteen months we intend to explore earlier lines of therapy, additional therapeutic areas, and combinations."

TRANSCEND is an open-label, multicenter Phase 1 study to determine the safety, pharmacokinetics, and antitumor activity of JCAR017 in adult patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B, and mantle cell lymphoma.

The data were based on a cutoff date of October 9, 2017 and presented by Jeremy Abramson, M.D., of Massachusetts General Hospital, who is a Principal Investigator for the TRANSCEND study. They add to those disclosed on November 1, 2017 in ASH (Free ASH Whitepaper) Abstract #581.

As with previous readouts, the TRANSCEND data were presented for both the core and full groups. The core group (N=67) includes 29 patients who received dose level two (DL2 = 100 million cells), 34 patients who received dose level one (DL1 = 50 million cells), and 4 patients who received dose level one twice, approximately 14 days apart.

The core group includes patients with DLBCL (NOS and transformed from follicular lymphoma) who are ECOG Performance Status 0-1. These patients represent a high-risk patient population, with approximately 90% of treated patients having one or more predictors of poor survival, including double or triple hit lymphoma, being chemorefractory to front-line or subsequent therapies, never reaching a complete remission with prior treatments, or never having undergone an autologous transplant. Enrollment of the pivotal cohort is ongoing with the core group at DL2.

The full analysis group represents evaluable r/r patients in the DLBCL cohort (N=91), which includes an additional 24 patients with poor performance status (ECOG Performance Status 2) or with niche subtypes of aggressive NHL. In both analysis groups all efficacy data are based on at least one month of follow-up with a 28-day restaging scan and all safety evaluable data are based on having received JCAR017 (liso-cel) with at least one month of follow-up. Product was available for 98% (126/128) of patients apheresed in the DLBCL cohort.

"The results of this study continue to show the exciting potential of this CAR T therapy," said Jay Backstrom, Chief Medical Officer and Global Head of Regulatory Affairs for Celgene. "Our collaboration with Juno reflects our commitment to delivering transformational treatments to patients with blood cancers such as non-Hodgkin lymphoma."

Topline data from the presentation as of the October 9, 2017 data cutoff date included:

Responses in core group

At DL2, the data showed a 3 month overall response rate (ORR) of 74% (14/19) and a 3 month complete response (CR) rate of 68% (13/19). Of patients that have reached 6 months of follow-up, 50% (7/14) were in CR. Across doses, 80% (16/20) of patients with CR at 3 months stayed in CR at 6 months, and 92% (11/12) of patients in response at 6 months remain in response as of data cutoff.
Across doses, median duration of response (DOR) was 9.2 months and median durability of CR was not reached.
Tolerability in core group

1% (1/67) experienced severe cytokine release syndrome and 15% (10/67) experienced severe neurotoxicity.
36% (24/67) had any grade CRS and 21% (14/67) had any grade NT.
58% (39/67) had no CRS or NT of any grade.
At dose level 1, 3% (1/34) experienced severe CRS and 21% (7/34) experienced severe NT.
At dose level 2, 0% (0/29) experienced severe CRS and 7% (2/29) experienced severe NT.
13% (9/67) received tocilizumab and 18% (12/67) received corticosteroids.
Tolerability across doses in full group

1% (1/91) experienced severe CRS and 12% (11/91) experienced severe NT.
35% (32/91) had any grade CRS and 19% (17/91) had any grade NT.
60% (55/91) had no CRS or NT of any grade.
The most common treatment-emergent adverse events (TEAEs) other than CRS and NT that occurred at ≥25% included neutropenia (49%), anemia (38%), fatigue (37%), thrombocytopenia (29%), nausea (27%), and diarrhea (25%). The most common TEAEs were similar between core and full groups.
JCAR017 (liso-cel) is a defined composition CD19-directed CAR T cell product candidate using a 4-1BB costimulatory domain. Juno believes JCAR017’s clinical profile could enable outpatient administration. A biologics license application filing is expected to be completed in the second half of 2018, with approval as early as the end of 2018.

ASH Investor and Analyst Event and Webcast

The Juno ASH (Free ASH Whitepaper) Investor and Analyst Event and webcast will be held Monday, December 11, 2017 at 8:30 p.m. Eastern Time. The webcast can be accessed live on the Investor Relations page of Juno’s website, www.JunoTherapeutics.com, and will be available for replay for 30 days following the event.