Juno Therapeutics Highlights Data and Presentations Supporting Best-in-Class Strategy for JCAR017 at ASH
—Updated JCAR017 (liso-cel) data in core group at dose level 2 showed 74% (14/19) ORR and 68% (13/19) CR rate at 3 months, with 50% (7/14) CR at 6 months—
—JCAR017 data continue to support better responses at dose level 2 without increased toxicity observed for CRS and NT compared to dose level 1 in core group—
“Juno presented a wide range of data and new insights at ASH, including
updated data in the TRANSCEND trial,” said
During ASH, Juno also announced that JCAR017 had received the
Updated Data from TRANSCEND Trial of JCAR017
Data from the TRANSCEND study of JCAR017 (liso-cel) in patients with
relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma
Data were based on a cutoff date of
Enrollment of the pivotal cohort is ongoing with the core group at dose level 2, one of multiple previously evaluated doses.
- In the core group at dose level 2 (DL2=100 million cells), 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 in core group with CR at 3 months stayed in CR at 6 months, and 92% (11/12) of patients in response at 6 months remained in response as of the data cutoff date.
- In the core group, 1% (1/67) experienced severe cytokine release syndrome and 15% (10/67) experienced severe neurotoxicity. 58% (39/67) had no CRS or NT of any grade.
- In the full group, 1% (1/91) experienced severe CRS and 12% (11/91) experienced severe 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% in the full group 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.
Juno believes JCAR017’s safety 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.
Oral Presentations on JCAR017 Translational Insights
Two additional oral presentations reported new clinical correlates, and safety and efficacy insights associated with JCAR017.
- Baseline patient characteristics, including high tumor burden and markers of inflammation, were associated with high CAR T cell expansion and increased rates of CRS and NT.
- Data showed an approximately 8-fold increased risk for CRS and NT in patients with high baseline tumor burden.
- Baseline markers of inflammation were associated with more durable responses; with respect to tumor burden the association was less pronounced.
On the same day,
- JCAR017 cells infiltrated tumors, and more infiltration trended with better response. At disease progression, tumors tended to express CD19 and lack CAR T cells.
- In patients whose disease progressed, no single resistance pathway appeared to be upregulated in the tumor at the time of progression, but well-known pathways such as PD-L1 and IDO were upregulated in different patients, suggesting that combinations with other immunotherapies may be beneficial.
8 patients had received JCAR017 as an outpatient at multiple trial sites and were evaluable with 28 or more days post-infusion. Compared to inpatient administration, outpatient administration showed an approximate 40% reduction in hospital days. 88% (7/8) of patients remained outpatient for at least 3 days post CAR T administration.
The goal of JCAR017 outpatient administration is to increase access and reduce hospitalization days without impacting safety. Juno anticipates generating additional data to evaluate this potential both as part of the TRANSCEND trial and in additional studies.
Pharmacodynamics of JCAR017
In a presentation on
Furthermore, an increase in CD8+ cell expansion was observed at dose level two compared to dose level one. Preliminary modeling suggests a potential therapeutic window for CAR T expansion may exist that limits toxicity and optimizes for durable response. Findings suggested that patient factors and tumor characteristics, apart from JCAR017 itself, are important to expansion and thus potentially response.
Manufacturing of JCAR017
In a poster presentation on
- A precise, consistent flat dose of administered CD4+ and CD8+ CAR T cells within +/- 8% of target cell count.
- Control and optimization of CD4+ and CD8+ T cell culture conditions that result in low between-drug product lot variability of phenotypes (e.g., CCR7) and in vitro function (e.g., IL-2, TNF-α and IFN-γ production after antigen stimulation).
- Constant formulation and volume of drug product that contributes to consistent cell health.
Controls result in a commercial manufacturing process expected to be successful >95% with a consistent turnaround time <21 days.
Multiple Myeloma Presentations
Poster presentations showing preclinical data highlighted early, encouraging insights into the design of BCMA-directed CAR T cells. Juno plans to present additional data on its BCMA program and strategy next year. The presentations at ASH highlighted Juno’s fully human binder, and showed that the inhibition of TGFβ signaling and combination strategies with Lenalidomide may contribute to a potential best-in-class product for multiple myeloma.
Juno Therapeutics is building a fully integrated biopharmaceutical
company focused on developing innovative cellular immunotherapies for
the treatment of cancer. Founded on the vision that the use of human
cells as therapeutic entities will drive one of the next important
phases in medicine, Juno is developing cell-based cancer immunotherapies
based on chimeric antigen receptor and high-affinity T cell receptor
technologies to genetically engineer T cells to recognize and kill
cancer. Juno is developing multiple cell-based product candidates to
treat a variety of B-cell malignancies as well as multiple solid tumors
and multiple myeloma. Several product candidates have shown compelling
clinical responses in clinical trials in refractory leukemia and
lymphoma conducted to date. Juno’s long-term aim is to leverage its
cell-based platform to develop new product candidates that address a
broader range of cancers and human diseases. Juno brings together
innovative technologies from some of the world’s leading research
institutions, including the Fred Hutchinson Cancer Research
Center, Memorial Sloan Kettering Cancer Center, Seattle Children’s
About The Juno-Celgene Collaboration
This press release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995, Section
27A of the Securities Act of 1933, and Section 21E of the Securities
Exchange Act of 1934, including statements regarding Juno’s mission,
progress, and business plans; clinical or translational data and the
implications thereof; the timing of regulatory submissions or approvals;
clinical trial plans; the potential best-in-class profile for JCAR017
(liso-cel); the potential for outpatient administration of JCAR017;
Juno’s ability to harness its investments to better characterize and
improve current and future CAR T products and product candidates for
patients; the importance of controlling product composition; expected
success rates and turnaround time for manufacturing; the potential of
JCARH125 to be a best-in-class product; and the potential of the