Priority Review BLA of Epcoritamab for R/R Large B-Cell Lymphoma
The FDA has accepted for Priority Review the Biologics License Application (BLA) for subcutaneous epcoritamab, an investigational bispecific antibody, for the treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. Under the Prescription Drug User Fee Act, the FDA has set a target action date of May 21, 2023.
The BLA submission is based on safety and preliminary efficacy data from the LBCL cohort of the pivotal EPCORE NHL-1 open-label, multi-center, Phase II clinical trial evaluating epcoritamab in patients with relapsed, progressive, or refractory CD20+ mature B-cell non-Hodgkin lymphoma (B-NHL). These results were presented in a late-breaking oral presentation as a part of the Presidential Symposium at the European Hematology Association Annual Meeting in Vienna, Austria.
EPCORE NHL-1 is an open-label, multi-center, safety and preliminary efficacy trial of epcoritamab, including a Phase I first-in-human, dose-escalation part; a Phase II expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive, or refractory CD20+ mature B-NHL, including LBCL and DLBCL. Data from the dose-escalation part of the study, which determined the recommended Phase II dose, were published in The Lancet in 2021. In the Phase II expansion part, additional patients are treated with epcoritamab to further explore the safety and efficacy of epcoritamab in patients with different types of relapsed/refractory B-NHLs who had limited therapeutic options.
The primary endpoint of the Phase II expansion part was overall response rate as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity.
FDA Clearance of IND Application for CB-011 for Relapsed or Refractory Multiple Myeloma
The FDA approved clearance of an Investigational New Drug (IND) application for CB-011, a genome-edited allogeneic anti-BCMA CAR T-cell therapy with immune cloaking. The CaMMouflage Phase I clinical trial, a multicenter, open-label study, evaluated the safety and efficacy of a single dose of CB-011 in adult patients with relapsed or refractory multiple myeloma (r/r MM) and is expected to initiate patient enrollment for treatment at dose level 1 (50x106 CAR-T cells) in early 2023.
CB-011 is the second allogeneic cell therapy advancing into clinical development from a CAR T-cell platform targeting hematologic malignancies. The first allogeneic cell therapy, CB-010, an allogeneic anti-CD19 CAR T-cell therapy with a PD-1 knockout, is being evaluated in the ongoing ANTLER Phase I clinical trial in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Encouraging safety and antitumor activity for CB-010 at dose level 1 have been reported from the ANTLER trial.
"CAR T-cell therapies have shown great promise for treating patients with relapsed or refractory multiple myeloma," said Sundar Jagannath, MD, Director of the Multiple Myeloma Center of Excellence at Tisch Cancer Institute in Mount Sinai Medical Center. "Allogeneic or off-the-shelf CAR T-cell therapies would provide a great option for patients with multiple myeloma, helping to overcome the need for bridging therapies, as well as variable quality and manufacturing timelines of autologous CAR-T cells."
CB-011 is one of the first allogeneic anti-BCMA CAR T-cell therapy that is engineered to improve persistence of antitumor response through an immune cloaking genome-editing approach that removes the B2M protein and inserts a B2M-HLA-E fusion protein. CB-011 has four edits implemented via the Cas12a CRISPR hybrid RNA-DNA technology:
* Edits 1 and 2-A humanized anti-BCMA CAR is site-specifically inserted into the TRAC gene to target cancer cells, thereby knocking out expression of the T-cell receptor to reduce the risk of graft-versus-host disease.
* Edits 3 and 4-A B2M-HLA-E peptide fusion gene is site-specifically inserted into the B2M gene of the CAR-T cells to prevent recognition and rejection by patient T cells and blunt rejection by NK cells. These edits knock out endogenous B2M expression, eliminating endogenous HLA class I presentation and reducing T cell-mediated rejection, while enabling expression of B2M-HLA-E needed to inhibit NK cell-mediated rejection.
The CaMMouflage Phase I trial is an open-label, multicenter, clinical trial designed to evaluate CB-011 in adults with relapsed or refractory multiple myeloma (r/r MM). Part A, a 3+3 dose-escalation design, will evaluate the safety and tolerability of CB-011 at multiple dose levels and will be utilized to determine the maximum tolerated dose and/or the recommended Phase II dose. Part B is the dose-expansion portion with the primary objective of determining tumor response after a single dose of CB-011. CaMMouflage will include patients who have had three or more prior lines of therapy and will exclude patients who have received a BCMA-targeted therapy within the last 3 months and/or any prior CAR T-cell therapy.
FDA Approval of Lymphatic Tracer for All Breast Cancer Staging Procedures
The Magtrace lymphatic tracer can now be used for all patients undergoing breast cancer surgery. It is the first tracer specifically designed to optimize the breast cancer staging procedure, sentinel lymph node biopsy. It helps surgeons determine if the tumor has spread beyond the breast by precisely identifying the first draining or sentinel lymph nodes in the armpit for further analysis.
Previously, the lymphatic tracer was approved for patients undergoing a mastectomy procedure. Since then, additional data submitted to the FDA has validated its use for all breast cancer patients. This now expands the treatment to all patients choosing breast-conserving surgery.
One of the greatest advantages of the lymphatic tracer over the current standard practice of using a radioactive tracer combination is that it is not limited by nuclear medicine supply chain issues. This means there is no need for hospitals to suffer delays to or cancellations of cancer patient surgeries.
"What originally drew me to [this product] were the huge benefits it could provide to our patients, including eliminating the pain of a radioactive injection and reducing unnecessary surgery. I truly believe that with this news, there is no reason why it shouldn't become the new standard of care for sentinel lymph node biopsy," said Michael Alvarado, MD, Professor of Surgery at UCSF. "This much-anticipated approval allows any surgeon, regardless of hospital setting, to offer their patients the best standard of treatment in breast cancer staging. For the first time in the U.S., operating departments will not have to rely on nuclear medicine before they can operate on their patients."