At the 60th American Society of Hematology (ASH) Annual Meeting
CAR T is Still a Star
With all the pessimistic views critics have sprayed around in the past few years about the cell therapy for cancer, the CAR T approach remained a star of prominent cancer gatherings. This phenomenon confirms the value of the FDA decision of approving the CAR T products, in spite of their life-threatening side effects which include the cytokine release syndrome as well as others. With regard to the CAR T inability to deal with solid tumors, companies woh paid billions of dollars to acquire CAR T developing firms such as Juno and Kite, seem to have been convinced that improving on the CAR T will enable solving this problem as well.
In the ongoing ASH 18, the CAR T captured the minds of oncologists in spite of the fact that the adverse events (AEs) of the treatment were not totally erased. However, oncologists were capable of developing protocols for managing the AEs as demonstrated in recent clinical trials.
The great enthusiasm was for the results which continue to demonstrate a high percentage of responses including complete responses (CRs) and overall response rates (ORR), in addition to the durability of the treatments and their positive results.
In January 2018, Celgene Corporation (CELG) acquired Juno at approximately $9 billion. Juno is a pioneer in the chimeric antigen receptor T (CAR T and T cell receptor (TCR)) therapeutics. Juno’s pipeline comprised novel CAR T products with multiple targets for cancer indications. The acquisition added to Celgene’s pipeline, JCAR017 (lisocabtagene maraleucel; liso-cel), which represents a potentially best-in-class CD19-directed CAR T for refractory diffuse large B-cell lymphoma (DLBCL).
Initial Phase 1/2 Data in Relapsed/Refractory CLL, Including Those with
High-Risk Disease Previously Treated with Ibrutinib
At ASH, Celgene announced initial data from the dose-escalation part of the ongoing, open-label multicenter Phase 1/2 TRANSCEND CLL-004 study of JCAR017. The beneficiaries were patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), including patients with cytogenetic features of a high-risk disease who were previously treated with ibrutinib.
Data included 16 patients from the ongoing phase 1 monotherapy dose-escalation part of the study. The median number of lines of prior therapy was 4.5, and 75% of patients had high-risk cytogenetic features.
All patients had previously received treatment with ibrutinib, 81% had relapse/refractory disease on ibrutinib and 50% received prior treatment with ibrutinib and venetoclax. Following lymphodepletion with fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2) for three days, patients received liso-cel at dose level 1 (5×107 CAR+ T cells) or dose level 2 (1×108 CAR+ T cells).
The ORR was 81%, with 43% of patients demonstrating a CR. As of September 2018, five patients have a six-month follow-up, and all demonstrated undetectable minimal residual disease (uMRD) in the blood. The CAR T cells remained detectable in the patients at three months.
Alise Reicin, M.D., President, Global Clinical Development for Celgene stated, “Ibrutinib is a standard of care for patients with CLL, but outcomes are poor for patients whose disease progresses on or after ibrutinib. These initial findings support further research with liso-cel in CLL and reinforce Celgene’s commitment to cellular therapy across a broad spectrum of blood cancers.”
Tanya Siddiqi, M.D., City of Hope National Medical Center explained, “In CLL, undetectable MRD correlates with improved outcomes for patients and is particularly difficult to achieve in patients who have progressed on ibrutinib. The high response rates we observed in heavily pretreated patients in this initial data set, along with undetectable MRD status, that appears to be maintained over time, warrants further investigation of liso-cel in this area of high unmet need.”
Liso-cel is not approved in any country.
Celgene’s lead CAR T trial, TRANSCEND NHL-001, is studying liso-cel in adult patients with relapsed or refractory diffuse large B cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B, and mantle cell lymphoma.
Initial Clinical Data from Ongoing Phase 1/2 EVOLVE Trial
with Anti-BCMA CAR T Therapy JCARH125 in Relapsed/Refractory Multiple Myeloma
Results were presented in an oral presentation at the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA (Abstract #957).
On Dec. 3rd, Celgene announced initial safety data from its ongoing proof-of-concept trial of JCARH125 in patients with relapsed/refractory multiple myeloma. JCARH125 is an investigational BCMA-targeting CAR T cell therapy.
The data were from the phase 1/2 EVOLVE trial conducted on patients who have been treated with JCARH125 in the dose escalation study.
The patients enrolled in the study received at least three prior lines of multiple myeloma therapy, including an autologous stem cell transplant for transplant-eligible patients, a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Dose escalation is currently ongoing.
So, the patients in the trial were heavily pretreated with a median of seven prior lines of therapies (range, 3-23) and 77% had high-risk cytogenetics.
In this first report of JCARH125 data, the median follow up was only 11 weeks.
The Overall Response Rate was 82%.
At the lowest dose level, the ORR was 79% with 43% of patients achieving stringent complete response (sCR) or CR.
Commenting on the trial, Mark Gilbert, M.D., Chief Medical Officer for Juno Therapeutics representing Celgene, said, “We believe that cellular therapies targeting BCMA will play an important role in the future treatment of patients with multiple myeloma. These data from EVOLVE trial further support our commitment to innovation in multiple myeloma clinical research.”
JCARH125 is investigational and has not been approved in any country.
Operating inside Celgene, Juno’s scientists have done an impressive job improving the efficacy as observed in the CAR T JCAR017 JCARH125.
What makes the results so notable is the high overall response rates and complete response rates and durable remission in patients with resistant cancers and high-risk cytogenetic features.
The best is yet to come.
The improved results will definitely further improve, bringing excellent news for Celgene and the other firms developing CAR T. These include: Gilead (GILD), Novartis (NVS) and Cellectis (CLLS), which created its allogeneic CAR T product UCART 19 and licensed to Servier, who is developing it with Pfizer (PFE).
We believe that Celgene will not be a loser for paying around $9 billion for Juno. The FDA demonstrated enthusiasm for this targeted cellular treatment for cancer when it approved CAR-T therapeutics despite the severe problems that had to be solved. Visiting with the history of the CAR-T improvements in efficacy and its unprecedented positive results on resistant deadly cancers confirms our belief that this firm has done the right thing by bringing in the CAR T products. We also believe that this approach might be the best solution to the firm’s financial troubles.
Everybody knows that immuno-oncology through T cell products and other approaches will dominate cancer treatments.
We will post an article about Celgene’s presentations, of other products for other cancers, at the ASH meeting.
We are also assessing other presentations at the ASH meeting with regard to articles we will post under Today’s Highlights. These articles will include presentations from Amgen, Gilead, Novartis, and others.