Janssen Presents First Data from MajesTEC-2 Trial of TECVAYLI™ (teclistamab-cqyv) in Combination with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) and Lenalidomide in Relapsed or Refractory Multiple Myeloma

2022-12-11

临床结果上市批准临床1期免疫疗法ASH会议

Initial Phase 1b study results show clinical activity with immune-based triplet therapy regimen

NEW ORLEANS, LA, USA I December 10, 2022 I The Janssen Pharmaceutical Companies of Johnson & Johnson announced today new results from a cohort of the Phase 1b MajesTEC-2 study of TECVAYLI™ (teclistamab-cqyv), a first-in-class, BCMAxCD3 bispecific T-cell engager antibody, in combination with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) and lenalidomide. According to the results, the immune-based triplet therapy regimen had a manageable safety profile with no unexpected safety signals observed. A very good partial response (VGPR) or better was achieved by 90.3 percent of patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy, including a proteasome inhibitor proteasome inhibitor and immunomodulatory drug, with responses deepening over time.1 These data were presented during the 2022 American Society of Hematology (ASH) Annual Meeting (Abstract #160).

"These results show the potential of the combination of the bispecific BCMA-directed antibody teclistamab with the anti-CD38 antibody daratumumab and lenalidomide in the treatment of patients with relapsed or refractory multiple myeloma," said Emma Searle, M.D., Ph.D., Consultant Hematologist and Honorary Senior Lecturer, The Christie Hospital and University of Manchester, England, and study investigator.† "This is the first presentation of data from a teclistamab-based triplet regimen and we are eager to better understand how this combination may benefit patients through ongoing clinical studies."

At a median follow-up of 8.4 months (range, 1.1 to 12.9), the overall response rate (ORR) was 93.5 percent.1 Among all patients in the trial, VGPRs or better were achieved by 90.3 percent of patients, and 54.8 percent of patients achieved a complete response (CR) or better.1 Median time to response was one month, and responses deepened.1 The median time to CR or better was three months (range, 1 to 10.4).1 At data cut-off, 80.6 percent of patients remained progression-free and on treatment.1 Responses deepened over time, and median duration of response had not been reached.1

"Following the recent regulatory approvals of TECVAYLI in the U.S. and EU, as well as its inclusion in the NCCN Clinical Practice Guidelines in Oncology as a recommended treatment option for certain patients with multiple myeloma, we are encouraged by its potential to improve outcomes in combination regimens and for earlier lines of treatment," said Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research and Development, Janssen Research & Development, LLC. "We remain committed to addressing the unmet needs of patients with multiple myeloma through off-the-shelf immunotherapies like TECVAYLI and where we can bring together novel therapeutic approaches in the treatment of complex blood cancers."

The primary objective of this cohort of the MajesTEC-2 study (NCT04722146) was to understand if the immunomodulatory effects of daratumumab and lenalidomide could enhance the function of TECVAYLI™, resulting in enhanced antimyeloma activity in a broader population of patients.1 The MajesTEC-7 study (NCT05552222) will examine the potential of this combination in patients newly diagnosed with multiple myeloma.

The most frequent hematological adverse events (AEs) observed in the study included neutropenia (84.4 percent any grade, 78.1 percent grade 3/4) and thrombocytopenia (25 percent any grade, 15.6 percent grade 3/4).1 The most frequent non-hematological AE was cytokine release syndrome (CRS) (81.3 percent, all grade 1/2); 97 percent of CRS events occurred during cycle 1.1

Other common non-hematological AEs included fatigue (46.9 percent any grade, 6.3 percent grade 3/4); diarrhea (46.9 percent any grade, none grade 3/4); cough (40.6 percent any grade, 3.1 percent grade 3/4); COVID-19 (37.5 percent any grade, 12.5 percent grade 3/4); insomnia (37.5 percent any grade, 3.1 percent grade 3/4); hypophosphatemia (31.3 percent any grade, 6.3 percent grade 3/4); pyrexia (31.3 percent any grade, 3.1 percent grade 3/4); upper respiratory tract infection (31.3 percent any grade, none grade 3/4); increased alanine aminotransferase (ALT) (28.1 percent any grade, 9.4 percent grade 3/4) and pneumonia (25 percent any grade, 15.6 percent grade 3/4).1 Two patients discontinued therapy due to an AE (COVID-19), considered to be unrelated to the study by investigator assessment.1 Infections were common among patients in the study and the majority were low grade (90.6 percent any grade, 37.5 percent grade 3/4).1

New Data from the Phase 1/2 MajesTEC-1 Study Evaluating TECVAYLI™ in Relapsed or Refractory Multiple Myeloma Patients

New correlative analyses were also presented from the MajesTEC-1 study (NCT04557098). Data from these analyses may be used to help better understand baseline immune and tumor correlatives associated with outcomes in patients treated with TECVAYLI™.2 The data were presented during an oral abstract session (Abstract #97). Additional pharmacokinetic data evaluating potential drug interactions with TECVAYLI™ were presented during a separate poster session (Abstract #3228), as well as analyses of serum teclistamab-cqyv concentrations after intravenous and subcutaneous administration (Abstract #1911), to improve understanding of the clinical pharmacological profile of TECVAYLI™.3,4

About the MajesTEC-2 Study

MajesTEC-2 (NCT04722146); is Phase 1b multicohort study evaluating the safety and efficacy of TECVAYLI™ in combination with other anticancer therapies in patients with relapsed or refractory multiple myeloma who received at least one prior line of therapy.1 Patients were eligible for treatment if they had received 1-3 prior lines of therapy, including a proteasome inhibitor proteasome inhibitor and immunomodulatory drug.1

In the presented study cohort, 32 patients received weekly doses of TECVAYLI™ (0.72 mg/kg or 1.5 mg/kg, with step-up dosing) plus the approved schedules of DARZALEX FASPRO® 1800 mg and lenalidomide 25 mg.1 Responses were investigator assessed using International Myeloma Working Group criteria, and AEs were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except for CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), which were graded per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.1

About TECVAYLI™

TECVAYLI™ (teclistamab-cqyv) received approval from the U.S. Food and Drug Administration in October 2022 as an off-the-shelf (or ready to use) bispecific antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.5 In August 2022, TECVAYLI™ received approval from the European Commission as an off-the-shelf bispecific antibody administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor proteasome inhibitor, and an anti-CD38 antibody.6 Teclistamab-cqyv (TECVAYLI™) was recently recommended by the National Comprehensive Cancer Network® (NCCN®) as a treatment option for these patients. TECVAYLI™ is a first-in-class, bispecific T-cell engager antibody therapy which uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.7

About DARZALEX FASPRO®

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma (MM), three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.8 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.

About Multiple Myeloma Myeloma

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.9 In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.10 In 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.11 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, kidney problems or infections.12

Please read full Prescribing Information including Boxed Warning for TECVAYLI™.

DARZALEX FASPRO ® IMPORTANT SAFETY INFORMATION

INDICATIONS

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

Please see full Prescribing Information for DARZALEX FASPRO®.

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at @JanssenGlobal and @JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

†Dr. Searle has served as a consultant to Janssen; she has not been paid for any media work.

SOURCE: Janssen