Johnson & Johnson Announces Positive Results from Phase 3 CARTITUDE-4 Study of Carvykti to Treat Relapsed or Lenalidomide-Refractory Multiple Myeloma

Johnson & Johnson announced positive results from a prespecified second interim analysis of the phase 3 CARTITUDE-4 study evaluating Carvykti (ciltacabtagene autoleucel; cilta-cel) compared to standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) for the treatment of patients with relapsed or lenalidomide-refractory multiple myeloma after one prior line of therapy. The interim analysis showed a statistically significant and clinically meaningful improvement in overall survival (OS) for patients treated with Carvykti versus standard therapies. Safety data were consistent with the approved label.

"Carvykti, a one-time infusion, is now the first cell therapy to significantly improve overall survival versus standard of care for patients with myeloma as early as second line," said Jordan Schecter, M.D., vice president, disease area leader, multiple myeloma, Johnson & Johnson Innovative Medicine. "As we continue to strive to change outcomes and advance care for every person living with multiple myeloma, we're excited to share these results, which add to the growing body of evidence across our portfolio of differentiated, complementary therapies that attack the disease in different ways throughout the course of a patient's journey."

Updated results will be presented at an upcoming medical meeting and submitted to regulatory authorities worldwide.

CARTITUDE-4 (NCT04181827) is the first randomized phase 3 study evaluating the efficacy and safety of Carvykti. The study compares Carvykti with standard of care treatments PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy. The primary endpoint of the study is progression-free survival (PFS); safety, OS, minimal residual disease negative rate and overall response rate are secondary endpoints.

Carvykti (cilta-cel) received US Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. In April 2024, Carvykti was approved in the US for  treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and who are refractory to lenalidomide, following a unanimous (11 to 0) FDA Oncologic Drugs Advisory Committee (ODAC) recommendation in support of this new indication. In April 2024, the European Medicines Agency (EMA) approved a Type II variation for Carvykti for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. In September 2022, Japan's Ministry of Health, Labour and Welfare (MHLW) approved Carvykti for the treatment of adults with relapsed or refractory multiple myeloma in patients that have no history of CAR-positive T cell infusion therapy targeting BCMA and who have received three or more lines of therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody, and in whom multiple myeloma has not responded to or has relapsed following the most recent therapy.

Carvykti is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR-positive T cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The Carvykti CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize Carvykti.

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow. In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumours. Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease. In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the US and more than 12,000 people would die from the disease. People living with multiple myeloma have a 5-year survival rate of 59.8 per cent. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.

Carvykti (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.