J & J Announces New Results from Phase 1b RedirecTT-1 Study of Talvey & Tecvayli

J & J Announces New Results from Phase 1b RedirecTT-1 Study of Talvey & Tecvayli

By, Admin 1 October 2024

Johnson & Johnson announces updated results from phase 1b RedirecTT-1 study of Talvey & Tecvayli in patients with RRMM including those with extramedullary disease

Overview

Johnson & Johnson announced updated results from the investigational phase 1b RedirecTT-1 study evaluating the first-ever bispecific antibody combination of Talvey (talquetamab-tgvs), the first and only FDA-approved bispecific targeting GPRC5D, and Tecvayli (teclistamab-cqyv), the first FDA-approved BCMA-directed bispecific therapy, showing high response rates and durable responses, with a consistent safety profile to each monotherapy, in patients with relapsed or refractory multiple myeloma (RRMM) who were triple-class exposed, including those with extramedullary disease. These data were featured in an oral presentation at the 2024 International Myeloma Society Annual Meeting (Abstract # OA – 03).

Word from Principal Study Investigator

  • As multiple myeloma progresses, it becomes more difficult to treat, especially in patients with extramedullary disease, which spreads beyond the bone marrow and typically becomes resistant to standard therapies,"" said Yael Cohen, M.D., head of myeloma unit, Hematology Institute, Tel Aviv Sourasky Medical Center, Israel, and principal study investigator. 
  • These results reflect promising efficacy and a manageable safety profile for this combination of two first-in-class, innovative bispecific therapies and provide a potentially promising off-the-shelf option for patients with advanced multiple myeloma.

The Procedure

  • At data cutoff, 44 patients had been treated with the recommended phase 2 regimen (RP2R) of 0.8 mg/kg of Talvey in combination with 3 mg/kg of Tecvayli every other week, the overall response rate (ORR) was 79.5 per cent.  
  • With a complete response or better (CR+) rate of 52.3 per cent, an 18-month duration of response (DOR) of 85.9 per cent, and an 18-month progression-free survival (PFS) rate of 69.8 per cent with median follow-up of 18.2 months.

The Outcomes

  • Results from a subgroup analysis of patients with extramedullary disease (EMD; =1 bone-independent lesion of =2 cm), a patient population often facing limited treatment options, demonstrated meaningful ORR and DOR for bispecific antibody-based treatment. 
  • At the RP2R (n=18), results showed an ORR of 61.1 percent, with CR+ rate of 33.3 percent, an 18-month DOR of 81.8 percent, and an 18-month PFS rate of 52.9 per cent in patients with EMD at median follow-up 13.6 months.

Safety Profile of the Combo

  • The combination of Talvey and Tecvayli had a safety profile that was consistent with the known safety profiles of each agent as monotherapy. 
  • Cumulative incidence of Grade 3/4 infections was slightly higher than that seen with either agent as monotherapy but plateaued from six months, and non-hematologic adverse events were generally low grade, including taste (50 per cent) and non-rash skin (56.8 per cent) and nail (47.7 per cent) AEs, with no discontinuations due to cytopenias.

Statement from Johnson & Johnson

  • Talvey and Tecvayli have already demonstrated powerful efficacy as standalone therapies as first-in-class bispecifics in the clinical and real-world settings,"" said Jordan Schecter, M.D., vice president, disease area leader, multiple myeloma, Innovative Medicine at Johnson & Johnson. 
  • We continue to research this innovative combination, as this study demonstrates both the efficacy and manageable safety profile of this combination, particularly in hard-to-treat patients such as those with EMD, as well as the combinability of Talvey with other effective therapies.

Presenting Data

  • Additional data underscoring the combinability of Talvey from the TRIMM-2 study will also be presented at IMS. 
  • First results from the RedirecTT-1 study were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The RedirecTT-1 trial

  • The RedirecTT-1 (NCT04586426) study is an ongoing phase 1b dose escalation study of the combination of the bispecific T-cell redirection antibodies Talvey and Tecvayli in patients (n=208) with relapsed or refractory multiple myeloma. 
  • The primary objective is to identify the recommended phase 2 regimen(s) (RP2R[s]) and schedule for the study treatment and to characterize the safety of the RP2R(s) for the study treatment. 
  • In part 1, patients will receive Talvey and Tecvayli with or without daratumumab in 28-day cycles following initial step-up doses. 
  • In part 2, patients will receive treatment doses (combination of Talvey and Tecvayli and daratumumab + Talvey + Tecvayli regimens) which will be determined by the recommended phase 2 regimen (s) (RP2R[s]) of the study treatment identified in Part 1. 
  • In part 3, patients will receive Talvey + Tecvayli combination therapy, at the RP2R selected from Part 1 and Part 2.

About the Cancer: Multiple Myeloma

  • Multiple myeloma is a blood cancer affecting a type of white blood cell called plasma cells found in the bone marrow. 
  • In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow. 
  • Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease. 
  • In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the US and more than 12,000 will die from the disease. 
  • People 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, kidney problems or infections.

FDA Approvals: Talvey

  • Talvey (talquetamab-tgvs) received approval from the US FDA in August 2023 as a first-in-class GPRC5D-targeting bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.
  • Since FDA approval, 1,500 patients were treated with Talvey. 

EMA Approvals: Talvey

  • The European Commission (EC) granted conditional marketing authorization (CMA) of Talvey (talquetamab-tgvs) in August 2023 as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.

Anout Talvey & CD3 Receptor

Talvey is a bispecific T cell engaging antibody that binds to the CD3 receptor expressed on the surface of T cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target which is highly expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as some healthy tissues such as epithelial cells of the skin and tongue.

Tecvayli Approval from FDA

  • Tecvayli (teclistamab-cqyv) received approval from the US FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM).
  • It is given to a patient who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody. 

Tecvayli Approval from EC

  • The European Commission (EC) granted Tecvayli conditional marketing authorization (CMA) in August 2022 as monotherapy for the treatment of adult patients with RRMM.
  • It is provided to the patients who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. 
  • In August 2023, the EC granted the approval of a Type II variation application for Tecvayli, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months. 

About Tecvayli

  • Tecvayli is a first-in-class, bispecific T cell engager antibody therapy that 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. 

BLA for Tecvayli

In February 2024, the US FDA approved the supplemental Biologics License Application (sBLA) for Tecvayli for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months.

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