Top news of the week in oncology and cancer drug development.
CTL019 Highly Effective in Global Phase II ALL Study
The CAR T-cell therapy CTL019 demonstrated an 82% complete remission or CR with incomplete blood count recovery rate for pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia. The phase II study enrolled patients at 25 centers in the United States, Europe, Asia, and Australia.
In the first 50 patients enrolled, the CR rate was 68% and the CRi rate was 14%. All patients with a CR/CRi also tested negative for minimal residual disease (95% CI, 69-91; P <.0001). The 6-month overall survival rate was 89% (95% CI, 76-95) and the disease-free survival rate was 60%.
See more http://www.onclive.com/conference-coverage/ash-2016/ctl019-highly-effective-in-global-phase-ii-all-study-fda-submission-anticipated
Anti-CD22 CAR T-Cell Salvage Therapy Succeeds in Pediatric ALL
Anti-CD22 chimeric antigen receptor T-cell therapy induced an 80% complete remission rate among children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia, many of whom had prior anti-CD19 CAR T-cell therapy. The high remission rate occurred in patients who received biologically active dose levels of the treatment.
According to the findings, which were presented at the 2016 ASH Annual Meeting, the remissions were sustained, with 3 patients in ongoing remission now at 3 months, 6 months, and >1 year.
See more http://www.onclive.com/conference-coverage/ash-2016/anticd22-car-tcell-salvage-therapy-succeeds-in-pediatric-all
KTE-C19 Responses Spark FDA Submission for Aggressive Lymphomas
Treatment with the CD19-directed CAR T-cell therapy KTE-C19 showed a complete remission rate of 73% for patients with aggressive, chemorefractory primary mediastinal B-cell lymphoma and transformed follicular lymphoma. The objective response rate with the CAR T-cell therapy was 91% and all CRs occurred within the first month of treatment. After 3 months, both the CR and ORR rates were 64%.
Cytokine release syndrome occurred in 91% of patients, which was primarily low-grade; however, there was 1 death related to cardiac arrest in the setting of CRS. A biologics license application is expected to be fully submitted by the end of the first quarter of 2017 for patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant.
See more http://www.onclive.com/conference-coverage/ash-2016/ktec19-shows-high-cr-rate-in-aggressive-lymphoma-subtypes
Anti-BCMA CAR T-Cell Therapy Approaches 80% Response in Myeloma
An investigational anti—BCMA chimeric antigen receptor T-cell therapy demonstrated an objective response rate of 78% in patients with relapsed/refractory multiple myeloma. As of the data cutoff date, November 18, 2016, the ORR was 33% at the lowest dose, followed by a 100% ORR in higher dose cohorts.
See more http://www.onclive.com/web-exclusives/antibcma-car-tcell-therapy-approaches-80-response-in-myeloma
Pembrolizumab Combo Highly Effective for Heavily Pretreated Myeloma
Treatment with the combination of pembrolizumab, pomalidomide, and dexamethasone demonstrated promising durable efficacy and a tolerable safety profile for patients with relapsed/refractory multiple myeloma. In the single-center trial, the overall response rate was 65% with the pembrolizumab-containing triplet regimen.
Overall, 29% of patients experienced a very good partial remission or better. The stringent complete remission rate was 7% and the CR rate was 2%. Responses remained consistent in those with double-refractory disease and for those with high-risk cytogenetics.
See more http://www.onclive.com/conference-coverage/ash-2016/pembrolizumab-pomalidomide-combo-highly-effective-for-myeloma
Nivolumab/Ibrutinib Combo Shows Promise for Richter Transformation
Treatment with the combination of nivolumab and ibrutinib showed encouraging activity and safety in a small phase II study of patients with chronic lymphocytic leukemia and Richter transformation. In the small ongoing 13-patient study, the overall response rate (ORR) was 80% for ibrutinib plus nivolumab in patients with relapsed/refractory CLL, which Jain labeled as modest. In those with RT, the combination elicited a more promising ORR of 60%, which included 2 complete responses (CR).
See more http://www.onclive.com/conference-coverage/ash-2016/nivolumab-ibrutinib-combo-shows-promise-for-richter-transformation
Impressive Brentuximab Vedotin Data May Change Practice in CTCL
Brentuximab vedotin induced responses lasting at least 4 months in 56% of patients with cutaneous T-cell lymphoma versus 13% in patients receiving physician’s choice of standard therapies (P <.0001). At a median follow-up of 17.5 months, the median PFS was 16.7 months with brentuximab vedotin versus 3.5 months with physician’s choice (HR, 0.270; 95% CI, 0.169-0.430; P <.0001).
The ORR was 67% (n = 43) versus 20% (n = 13; P <.0001), with CR rates of 16% versus 2% (P = .0046), in the brentuximab vedotin and control arms, respectively.
See more http://www.onclive.com/conference-coverage/ash-2016/impressive-brentuximab-vedotin-data-may-change-practice-in-ctcl
Venetoclax Highly Effective With Bortezomib/Dexamethasone for Myeloma
Adding venetoclax to bortezomib and dexamethasone showed very promising efficacy and acceptable safety for patients with relapsed/refractory multiple myeloma. The triplet was especially effective in bortezomib non-refractory patients pretreated with 1 to 3 prior lines of therapy (n = 30), in whom the overall response rate (ORR) was 97%, according to data from the phase Ib study.
The stringent complete response (sCR) in this group was 10%, the CR rate was 23%, and the very good partial response (VGPR) was 41%. Across the full study, which included refractory patients (N = 66), the ORR was 67%.
See more http://www.onclive.com/conference-coverage/ash-2016/venetoclax-highly-effective-with-bortezomibdexamethasone-for-multiple-myeloma
BGB-3111 Response Rate Nears 100% in CLL/SLL
Treatment with the BTK inhibitor BGB-3111 had an objective response rate of 96% for patients with chronic lymphocytic leukemia and small lymphocytic leukemia. The ORR with BGB-3111 consisted entirely of partial responses (PRs; 67%) and PRs with lymphocytosis (28%). There were no complete responses at the time of the analysis. In those with high-risk molecular characteristics (del17p and/or del11q; n = 17), the ORR was 100%.
See more http://www.onclive.com/conference-coverage/ash-2016/bgb3111-response-rate-nears-100-in-cllsll
Ibrutinib Continues to Impress in Long-Term CLL/SLL Data
Findings from the longest follow-up to date evaluating up to 5 years of ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma show that the agent is safe and effective, with 89% of both treatment-naïve and relapsed patients experiencing a complete or partial response to the therapy. this included a complete response rate of 14% for all treated patients. In the TN group, ORR is 84%, and among R/R patients it is 86%.
See more http://www.onclive.com/conference-coverage/ash-2016/after-5-years-of-followup-ibrutinib-continues-to-impress-in-cllsll
FDA Grants Pembrolizumab Priority Review for Hodgkin Lymphoma
The FDA has granted a priority review to a supplemental biologics license application for pembrolizumab for use as a treatment for patients with refractory classical Hodgkin lymphoma or those who have relapsed after ≥3 lines of therapy. The application is based on results from the phase II KEYNOTE-087 and phase Ib KEYNOTE-013 trials. Under the priority review, the FDA is scheduled to make a final decision by March 15, 2017.
See more http://www.onclive.com/web-exclusives/fda-grants-pembrolizumab-priority-review-for-hodgkin-lymphoma
FDA Grants Ponatinib Full Approval for Rare Leukemias
The FDA has granted a full approval and label update to ponatinib for patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia for whom no other tyrosine kinase inhibitor therapy is indicated, as well as for patients with T315I-positive CML or T315I-positive Ph+ ALL.
The full approval is based on 4-year follow-up data from the phase II PACE trial, which evaluated ponatinib in patients with CML or Ph+ ALL who were refractory to dasatinib or nilotinib, or who harbored a T315I mutation. Among patients with CP-CML in the study, the major cytogenetic response rate was 55% and the major molecular response rate was 39%.
See more http://www.onclive.com/web-exclusives/fda-grants-ponatinib-full-approval-for-rare-leukemias
FDA Grants Priority Review to Avelumab for Merkel Cell Carcinoma
The FDA has granted a priority review to a biologics license application for avelumab as a treatment for patients with metastatic Merkel cell carcinoma. The priority review is based on data from the phase II JAVELIN Merkel 200 study. In the open-label trial, the objective response rate with avelumab was 31.8%, which included a 9.1% complete response rate.
After a median follow-up of 10.4 months, 82% of patients continued to respond to therapy. Under the priority review program, the FDA will decide on the BLA for avelumab within 6 months compared with the standard 10-month review.
See more http://www.onclive.com/web-exclusives/fda-grants-priority-review-to-avelumab-for-merkel-cell-carcinoma