CLINICAL AND REGULATORY
Legend’s Carvykti received FDA approval for treatment of multiple myeloma
Legend announced that FDA has approved its first product, Carvykti (cilta-cel), for the treatment of adults with relapsed or refractory multiple myeloma who have received four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen to develop and commercialize cilta-cel in 2017. Carvykti is a CAR-T therapy with two BCMA-targeting single domain antibodies and given as a one-time infusion with a recommended dose range of 0.5 to 1.0 x 106 CAR-positive viable T cells per kg of body weight. In the pivotal CARTITUDE-1 study, deep and durable responses were seen in patients with RRMM (n=97), with a high ORR of 98 %, including 78 % of the patients achieving stringent complete response. At a median of 18 months follow-up, the median duration of response was 21.8 months (95 percent CI 21.8-not estimable).
FDA accepted for Priority Review sBLA from BMS for Breyanzi for treatment of B cell lymphoma
FDA has accepted sBLA for Breyanzi (lisocabtagene maraleucel), a CD19-directed CAR-T cell therapy, to expand its current indication to include earlier use of Breyanzi for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL) after failure of first-line therapy. The FDA has granted the application Priority Review and assigned a PDUFA goal date of June 24, 2022. The sBLA is based on results from the Phase 3 TRANSFORM trial, a global, randomized, multicenter study evaluating Breyanzi as a second-line treatment in adults with relapsed or refractory LBCL compared to the standard of care consisting of salvage chemotherapy followed by high-dose chemotherapy plus autologous hematopoietic stem cell transplant.
Atara Bio announced patient death in its Phase 1 trial evaluating ATA2271
Atara reported Memorial Sloan Kettering Cancer Center’s (MSK) notification to FDA of a fatal serious adverse event associated with a patient treated in the ongoing Phase 1, MSK-conducted dose-escalation clinical study of autologous mesothelin CAR T, ATA2271. MSK has voluntarily paused enrollment of new patients in the study on a temporary basis while additional information regarding the case is gathered and reviewed. The FDA has notified MSK of its agreement with this approach. ATA2271 is a next-generation, autologous chimeric antigen receptor (CAR) T-cell therapy targeting mesothelin currently under clinical investigation in patients with malignant pleural mesothelioma. The single case involved a patient with a history of multiple malignancies and other comorbidities undergoing treatment for advanced recurrent mesothelioma. MSK is in the process of further evaluating the occurrence, including the extent of the relationship of the event to ATA2271.
Legend Biotech announced FDA clinical hold of its Phase 1 trial for LB1901
Legend Biotech announced that on February 11, 2022, the company was informed by the FDA that its Phase 1 clinical trial for LB1901 has been placed on clinical hold. LB1901 is the company’s investigational autologous CAR-T therapy targeting malignant CD4+ T-cells for the treatment of adults with relapsed or refractory T-cell lymphoma. To date, one patient has been dosed in the clinical trial. Before receiving the FDA’s clinical hold communication, Legend Biotech had, in accordance with the protocol, paused the clinical trial due to low CD4+ T-cell counts in the patient’s peripheral blood and notified the FDA. The patient has not experienced drug-related serious adverse events (SAEs) and is being monitored in accordance with the protocol.
Celyad announced voluntrary paused of CYAD-101-002 Phase 1 trial
Celyad announced it has taken the decision to voluntarily pause the CYAD-101-002 Phase 1b trial. The trial is part of a collaboration with Merck & Co., evaluating the TIM-based allogeneic NKG2D CAR T cell investigational therapy CYAD-101 administered concurrently with FOLFOX chemotherapy, followed by Keytruda, in patients with refractory metastatic colorectal cancer. The company has received reports of two fatalities that presented with similar pulmonary findings. The company has decided to voluntarily pause dosing and enrollment of patients in the CYAD-101-002 trial to investigate these events. Celyad is currently investigating these reports and evaluating any similar events in additional patients treated on study.